Md Adnan1, Md Nazim Uddin Chy2, A T M Mostafa Kamal3, James W Barlow4, Mohammad Omar Faruque5, Xinzhou Yang6, Shaikh Bokhtear Uddin7. 1. Pharmacognosy and Phytochemistry Lab, Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh; College of Biomedical Science, Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: mdadnan@kangwon.ac.kr. 2. Pharmacognosy and Phytochemistry Lab, Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh. 3. Pharmacognosy and Phytochemistry Lab, Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh. Electronic address: mostafa@pharm.iiuc.ac.bd. 4. Department of Chemistry, Royal College of Surgeons, Dublin, Ireland. Electronic address: jambarlow@rcsi.ie. 5. Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chittagong 4331, Bangladesh. Electronic address: omf@cu.ac.bd. 6. School of Pharmaceutical Science, South-Central Universities for Nationalities, Wuhan, China. Electronic address: xzyang@mail.scuec.edu.cn. 7. Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chittagong 4331, Bangladesh. Electronic address: bokhtear@cu.ac.bd.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Holigarna caustica (Dennst.) is commonly used in traditional medicine to treat a variety of painful conditions such as eye irritation, inflammation, arthritis, skin diseases, cuts and wounds. AIM OF THE STUDY: The present study was undertaken to investigate the anti-nociceptive and anti-inflammatory activities of the methanol extract of H. caustica leaves and to elucidate its possible mechanism(s) of action. MATERIALS AND METHODS: Fresh leaves of H. caustica were collected, dried, and extracted with methanol (MEHC). MEHC was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate and tail immersion test) pain models. To determine the possible mechanism behind the anti-nociceptive activity of MEHC, the opioid antagonist naltrexone was used to evaluate the involvement of opioid receptors in the case of formalin, hot plate and tail immersion tests, while the involvement of the cGMP and ATP-sensitive K+ channel pathways were assessed using methylene blue and glibenclamide respectively, in the acetic acid-induced writhing test. In parallel, the carrageenan-induced paw oedema model was used to determine the anti-inflammatory potential of the extract. Exploratory and motor behaviours were evaluated by the open-field test. Various bioactive compounds potentially responsible for the anti-nociceptive and anti-inflammatory activities were ascertained using GC-MS analysis. RESULTS: MEHC showed strong, significant and dose-dependent anti-nociceptive activity in all chemical-induced and heat-induced pain models at all experimental doses. The association of opioid receptors with the observed anti-nociceptive effects was confirmed by using naltrexone. The cGMP and ATP-sensitive K+ channel pathway was also shown to be involved in the anti-nociceptive activity of MEHC. In addition, MEHC exhibited a dose-dependent inhibition of inflammatory oedema induced by carrageenan. MEHC was not connected with changes in either the locomotor activity or motor responses of mice. In a GC-MS analysis, 40 compounds were identified, among which twelve are documented bioactive compounds with potent analgesic and anti-inflammatory properties. CONCLUSIONS: Our current study revealed that MEHC possesses strong central and peripheral anti-nociceptive as well as anti-inflammatory activity. It may also be concluded that both opioid receptors as well as the cGMP and ATP-sensitive K+ channel pathway are involved in the anti-nociceptive mechanism of MEHC. This study rationalizes the ethnomedicinal use of H. caustica leaves in various painful conditions.
ETHNOPHARMACOLOGICAL RELEVANCE: Holigarna caustica (Dennst.) is commonly used in traditional medicine to treat a variety of painful conditions such as eye irritation, inflammation, arthritis, skin diseases, cuts and wounds. AIM OF THE STUDY: The present study was undertaken to investigate the anti-nociceptive and anti-inflammatory activities of the methanol extract of H. caustica leaves and to elucidate its possible mechanism(s) of action. MATERIALS AND METHODS: Fresh leaves of H. caustica were collected, dried, and extracted with methanol (MEHC). MEHC was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate and tail immersion test) pain models. To determine the possible mechanism behind the anti-nociceptive activity of MEHC, the opioid antagonist naltrexone was used to evaluate the involvement of opioid receptors in the case of formalin, hot plate and tail immersion tests, while the involvement of the cGMP and ATP-sensitive K+ channel pathways were assessed using methylene blue and glibenclamide respectively, in the acetic acid-induced writhing test. In parallel, the carrageenan-induced paw oedema model was used to determine the anti-inflammatory potential of the extract. Exploratory and motor behaviours were evaluated by the open-field test. Various bioactive compounds potentially responsible for the anti-nociceptive and anti-inflammatory activities were ascertained using GC-MS analysis. RESULTS:MEHC showed strong, significant and dose-dependent anti-nociceptive activity in all chemical-induced and heat-induced pain models at all experimental doses. The association of opioid receptors with the observed anti-nociceptive effects was confirmed by using naltrexone. The cGMP and ATP-sensitive K+ channel pathway was also shown to be involved in the anti-nociceptive activity of MEHC. In addition, MEHC exhibited a dose-dependent inhibition of inflammatory oedema induced by carrageenan. MEHC was not connected with changes in either the locomotor activity or motor responses of mice. In a GC-MS analysis, 40 compounds were identified, among which twelve are documented bioactive compounds with potent analgesic and anti-inflammatory properties. CONCLUSIONS: Our current study revealed that MEHC possesses strong central and peripheral anti-nociceptive as well as anti-inflammatory activity. It may also be concluded that both opioid receptors as well as the cGMP and ATP-sensitive K+ channel pathway are involved in the anti-nociceptive mechanism of MEHC. This study rationalizes the ethnomedicinal use of H. caustica leaves in various painful conditions.
Authors: Md Adnan; Md Nazim Uddin Chy; A T M Mostafa Kamal; Kazi Asfak Ahmed Chowdhury; Md Atiar Rahman; A S M Ali Reza; Md Moniruzzaman; Satyajit Roy Rony; Mst Samima Nasrin; Md Obyedul Kalam Azad; Cheol Ho Park; Young Seok Lim; Dong Ha Cho Journal: Biomolecules Date: 2020-04-06
Authors: Md Adnan; Md Nazim Uddin Chy; A T M Mostafa Kama; Md Obyedul Kalam Azad; Kazi Asfak Ahmed Chowdhury; Mohammad Shah Hafez Kabir; Shaibal Das Gupta; Md Ashiqur Rahman Chowdhury; Young Seok Lim; Dong Ha Cho Journal: Biomedicines Date: 2020-03-25