Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy
This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropat...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822003371 |
| _version_ | 1797366619028062208 |
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| author | Adnan Khan Feng Wang Bushra Shal Ashraf Ullah Khan Syeda Saniya Zahra Ihsan ul Haq Salman Khan Kannan RR Rengasamy |
| author_facet | Adnan Khan Feng Wang Bushra Shal Ashraf Ullah Khan Syeda Saniya Zahra Ihsan ul Haq Salman Khan Kannan RR Rengasamy |
| author_sort | Adnan Khan |
| collection | DOAJ |
| description | This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors. |
| first_indexed | 2024-03-08T17:07:19Z |
| format | Article |
| id | doaj.art-d58923307c234ebabd3cf9225a46999c |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:07:19Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-d58923307c234ebabd3cf9225a46999c2024-01-04T04:38:14ZengElsevierPharmacological Research1096-11862022-09-01183106392Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathyAdnan Khan0Feng Wang1Bushra Shal2Ashraf Ullah Khan3Syeda Saniya Zahra4Ihsan ul Haq5Salman Khan6Kannan RR Rengasamy7Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; DHQ Teaching Hospital Timergara, Lower Dir, KPK, PakistanDepartment of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, PR ChinaPharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Faculty of Health Sciences, IQRA University, Islamabad Campus, (Chak Shahzad), Islamabad, PakistanPharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Faculty of Pharmaceutical Sciences, Abasyn University, Peshawar, PakistanDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, PakistanDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, PakistanPharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Corresponding author at: Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.Laboratory of Natural Products and Medicinal Chemistry (LNPMC), Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, India; Corresponding author.This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors.http://www.sciencedirect.com/science/article/pii/S1043661822003371Diabetic neuropathyHealthy livesMedicalStreptozotocinAjugarin-INrf2/Keap1 |
| spellingShingle | Adnan Khan Feng Wang Bushra Shal Ashraf Ullah Khan Syeda Saniya Zahra Ihsan ul Haq Salman Khan Kannan RR Rengasamy Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy Pharmacological Research Diabetic neuropathy Healthy lives Medical Streptozotocin Ajugarin-I Nrf2/Keap1 |
| title | Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy |
| title_full | Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy |
| title_fullStr | Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy |
| title_full_unstemmed | Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy |
| title_short | Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy |
| title_sort | anti neuropathic pain activity of ajugarin i via activation of nrf2 signaling and inhibition of trpv1 trpm8 nociceptors in stz induced diabetic neuropathy |
| topic | Diabetic neuropathy Healthy lives Medical Streptozotocin Ajugarin-I Nrf2/Keap1 |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822003371 |
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