Abstract
Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3′,5,6,7,8-hexamethoxy-4′,5′-methylenedioxyflavone (1), 3,3′,4′,5′,5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4′,5′-dimethylenedioxy-3,5,3′-trimethoxyflavone (3), and 3,3′,4′,5,5′,8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified from N. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1, 3, and 4 (12.5–25 mg/kg b.w.) exhibited dose-dependent and significant (p < 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+ channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1, 3, and 4 (12.5 mg/kg b.w.) demonstrated significant (p < 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAA receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5–25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1–4) from N. Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents.
Highlights
Pain is an unpleasant sensory perception accompanied by physiological damage comprising actual or potential tissue injury
Repeated chromatographic separation and purification of the methanol (MeOH) extract of N. plumbaginifolia leaves led to the isolation and characterization of 3,3′,5,6,7,8hexamothoxy-4′,5′-methylenedioxyflavone (1), 3,3′,4′,5′,5,6,7, 8-octamethoxyflavone (2), 6,7,4′,5′-dimethylenedioxy3,5,3′-trimethoxyflavone (3), and 3,3′,4′,5,5′,8-hexamethoxy-6,7methylenedioxyflavone (4) (Figure 1), the experimental details and structural data of which are available in the literature (Shajib et al, 2017)
The inhibition of total writhing episodes was dependent on dose and maximum inhibition of 59.77, 31.68, 24.59, 54.90, and 29.29% was seen for diclofenac and compounds 1–4, respectively
Summary
Pain is an unpleasant sensory perception accompanied by physiological damage comprising actual or potential tissue injury (de Sousa, 2011) Such sensation relies on individual’s emotional state and can be exacerbated by the psychological disorders like anxiety and depression. It adversely affects the quality of life and is one of the common reasons for visiting physicians and taking medications (de Santana et al, 2015). Polymethoxyflavones (PMFs) are exclusively found in citrus peels (Li et al, 2009) and some other pharmacologically significant plants (Kinoshita and Firman, 1996; Chen et al, 2011; Faqueti et al, 2016) They belong to the superfamily of flavonoids which can be classified as anthoxanthins (e.g., flavones, flavonols), flavanones, flavanonols, flavans, and anthocyanidins. Scientific studies revealed that PMFs might exert prominent in vivo or in vitro anti-nociceptive (Nadipelly et al, 2016), anti-inflammatory, anticarcinogenic (Li et al, 2009), cancer chemopreventive (Walle, 2007), sedative (Jin et al, 2012), anti-depressant, anxiolytic as well as benzodiazepine binding effects (Paladini et al, 1999; Abdelhalim et al, 2015) and possess excellent absorption and oral bioavailability (Li et al, 2009)
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