Antinociceptive activity of petroleum ether fraction obtained from methanolic extract of Clinacanthus nutans leaves involves the activation of opioid receptors and NO-mediated/cGMP-independent pathway

Zakaria, Zainul Amiruddin; Rahim, Mohammad Hafiz Abdul; Sani, Mohd Hijaz Mohd; Omar, Maizatul Hasyima; Ching, Siew Mooi; Kadir, Arifah Abdul; Ahmed, Qamar Uddin

doi:10.1186/s12906-019-2486-8

Cited by 11 publications

(11 citation statements)

References 47 publications

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“…Previous literatures have shown that in pain modulation, the opioid receptor is essential in the antinociceptive effect of many analgesic compounds. For instance, Zakaria et al 53 found out that petroleum ether extract of C. nutans exerted anti-nociceptive activity by activating opioid receptors and NO/cGMP pathway. Mehanna et al 54 investigated the anti-nociceptive effect of tadalafil in various pain models and revealed that the opioid receptors and NO/cGMP pathway were involved.…”

Section: Discussionmentioning

confidence: 99%

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Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor

Liu

Wang

et al. 2020

Exp Biol Med (Maywood)

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Diabetic neuropathic pain is a frequent complication of diabetic neuropathy. The specific manifestations of diabetic neuropathic pain include spontaneous pain and hyperalgesia, which seriously affect the quality of life of patients. Previous publications have shown that H2S has both pro-nociceptive and anti-nociceptive effects. This present investigation aimed to examine the anti-nociceptive effect of H2S on diabetic neuropathic pain. We established a diabetic neuropathic pain animal model with high-glucose, high-fat diet, and STZ, then treated rats with different concentrations of H2S and inhibitors of NOS, sGC, PKG, and opioid receptors. The mechanical allodynia and thermal hyperalgesia of rats were measured to assess the anti-nociceptive effects of H2S. The mRNA and protein expression of NOS and PKG1 were measured to explore their roles in the anti-nociceptive action of H2S. The results revealed that inhalation of H2S gas had anti-nociceptive effect in diabetic neuropathic pain model rats without affecting the blood glucose level and body mass. It increased the mRNA and protein level of nNOS, and the inhibitor of nNOS, 7-NI, abolished the anti-nociceptive effect of H2S. Furthermore, inhibitors of sGC and PKG could also abolish the anti-nociceptive effect of H2S. The expression of PKG1 was found to be increased by H2S, which was reversed by the inhibitors of nNOS, sGC, and PKG. Finally, CTOP, a μ-opioid receptor antagonist, abolished the anti-nociceptive effect of H2S, indicating that the μ-opioid receptor plays a role in the anti-nociceptive effect of H2S. In conclusion, the findings of this investigation suggest that hydrogen sulfide may attenuate the diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor. Impact statement There are currently approximately 425 million diabetic patients worldwide, of which approximately 90% of patients with diabetes suffer from neuropathy. Diabetic neuropathic pain (DNP) is a common complication of diabetic neuropathy. Nearly half of the patients hospitalized with diabetes have pain symptoms or symptoms related to neurological injury, and the incidence increases with age and diabetic duration. Anti-DNP analgesics have either limited therapeutic effects or serious side effects or lack of clinical trials, which has limited their application. Physiopathological mechanisms and treatment of DNP remain a significant challenge. The present confirmed that inhalation of H2S may attenuate the diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor. It provides us the animal study foundation for the application of H2S on the treatment of DNP and clarifies some target molecules in the pain modulation of DNP.

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Section: Discussionmentioning

confidence: 99%

“…For instance, Zakaria et al . 53 found out that petroleum ether extract of C. nutans exerted anti-nociceptive activity by activating opioid receptors and NO/cGMP pathway. Mehanna et al .…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor

Liu

Wang

et al. 2020

Exp Biol Med (Maywood)

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“…30 Another well-known model of thermal nociception, the hot-plate test was employed to check on the possible involvement of spinal, supraspinal pathways, and μ-opiate receptor agonists in regulation (CNS modulation) of pain response. 31 Both hot plate and tail immersion tests are extensively used for evaluating central anti-nociceptive activities. Opioid agents display their analgesic effects both via supra-spinal and spinal receptors.…”

Section: Discussionmentioning

confidence: 99%

Analgesic and Anti-Inflammatory Potential of Essential Oil of Eucalyptus camaldulensis Leaf: In Vivo and in Silico Studies

Mondal

Quispe

Sarkar

et al. 2021

Natural Product Communications

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The objective of our present study is to scrutinize the analgesic and anti-inflammatory potentials of essential oil of Eucalyptus camaldulensis leaf using different in vivo assay models at doses of 100, 200, and 400 mg/kg body weight. Twenty chemical compounds, which were isolated from the leaves essential oil of E. camaldulensis, were docked using AutodockVina against cyclooxygenase 2, tumor necrosis factor-α, and interleukin-1β convertase to elucidate the analgesic and anti-inflammatory activity. The essential oil of E. camaldulensis exhibited noteworthy analgesic activities in the writhing test. In the tail immersion and hot-plate test, the essential oil significantly extended the latency period. The number of licks in the formalin-induced paw licking test was markedly reduced following essential oil administration. In addition, E. camaldulensis essential oil revealed notable anti-inflammatory responses in carrageenan-induced paw edema, xylene induced ear edema and cotton pellet induced granuloma methods. Among 20 compounds, 5 ( cis-sabinol, globulol, α-eudesmol, β-eudesmol, and γ-eudesmol) showed better binding for cyclooxygenase-2 while β-eudesmol exhibited higher affinity for TNFα than that of TNF-alpha-IN-1 and standard drug. In the case of interleukin 1β convertase, maximum affinity was shown by α-eudesmol than the synthetic drug belnacasan. Chemical components of the essential oil interacted with diverse amino acid residues which were similar to the natural substrate and standard drugs. In conclusion, E. camaldulensis essential oil can be an effective source of analgesic and anti-inflammatory treatment and additional modification and docking studies will be required to justify the efficiency of globulol, α-eudesmol, β-eudesmol, and γ-eudesmol.

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“…The preparation of MECN was described in detail in our previous published study [9] while the procedures involved in the preparation of semipurified petroleum ether partition were described in detail by Zakaria et al [11].…”

Section: Methodsmentioning

confidence: 99%

“…The HPLC analysis was conducted at the Laboratory of Phytomedicine, Forest Research Institute of Malaysia, Kepong, Malaysia, according to the protocols described by Mahmood et al [14] but with slight modifications. The exact procedures were described in detail by Zakaria et al [11].…”

Section: Methodsmentioning

confidence: 99%

Antinociceptive Activity of Petroleum Ether Fraction ofClinacanthus nutansLeaves Methanolic Extract: Roles of Nonopioid Pain Modulatory Systems and Potassium Channels

Zakaria

Rahim

Roosli

et al. 2019

BioMed Research International

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Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been reported to exert antinociceptive activity. The present study aimed to elucidate the possible antinociceptive mechanisms of a lipid-soluble fraction of MECN, which was obtained after sequential extraction in petroleum ether. The petroleum ether fraction of C. nutans (PECN), administered orally to mice, was (i) subjected to capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged (intraperitoneal (i.p.)) with 0.15 mg/kg yohimbine, 1 mg/kg pindolol, 3 mg/kg caffeine, 0.2 mg/kg haloperidol, or 10 mg/kg atropine, which were the respective antagonist of α2-adrenergic, β-adrenergic, adenosinergic, dopaminergic, or muscarinic receptors; and (iii) prechallenged (i.p.) with 10 mg/kg glibenclamide, 0.04 mg/kg apamin, 0.02 mg/kg charybdotoxin, or 4 mg/kg tetraethylammonium chloride, which were the respective inhibitor of ATP sensitive-, small conductance Ca2+-activated-, large conductance Ca2+-activated-, or nonselective voltage-activated-K+ channel. Results obtained demonstrated that PECN (100, 250, and 500 mg/kg) significantly (P<0.05) inhibited all models of nociception described earlier. The antinociceptive activity of 500 mg/kg PECN was significantly (P<0.05) attenuated when prechallenged with all antagonists or K+ channel blockers. However, only pretreatment with apamin and charybdotoxin caused full inhibition of PECN-induced antinociception. The rest of the K+ channel blockers and all antagonists caused only partial inhibition of PECN antinociception, respectively. Analyses on PECN’s phytoconstituents revealed the presence of antinociceptive-bearing bioactive compounds of volatile (i.e., derivatives of γ–tocopherol, α–tocopherol, and lupeol) and nonvolatile (i.e., cinnamic acid) nature. In conclusion, PECN exerts a non-opioid-mediated antinociceptive activity involving mainly activation of adenosinergic and cholinergic receptors or small- and large-conductance Ca2+-activated-K+ channels.

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Antinociceptive activity of petroleum ether fraction obtained from methanolic extract of Clinacanthus nutans leaves involves the activation of opioid receptors and NO-mediated/cGMP-independent pathway

Cited by 11 publications

References 47 publications

Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor

Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor

Analgesic and Anti-Inflammatory Potential of Essential Oil of Eucalyptus camaldulensis Leaf: In Vivo and in Silico Studies

Antinociceptive Activity of Petroleum Ether Fraction ofClinacanthus nutansLeaves Methanolic Extract: Roles of Nonopioid Pain Modulatory Systems and Potassium Channels

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