Journal of ethnopharmacology · 2026
Ethnopharmacological validation of the antinociceptive potential of Calotropis gigantea L. flowers: Phytochemical characterization, safety evaluation, and mechanistic insights from in vivo models.
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Nazir Muhammad Muzammil, Sultana Salma, Rafique Azhar, Ashraf Asma
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea L. is traditionally used in South and Southeast Asia for the management of pain, inflammation, cough, burns, and other disorders. However, scientific evidence supporting its traditional use in pain management remains limited.
AIM OF THE STUDY: The present study aimed to evaluate the antinociceptive activity, safety profile, phytochemical composition, and possible mechanisms underlying the antinociceptive effects of the ethanolic extract of flowers of C. gigantea (CGEE).
MATERIALS AND METHODS: Phytochemical profiling was performed using qualitative screening, total phenolic and flavonoid assays, DPPH radical scavenging assay, and HPLC analysis. Acute and subacute oral toxicity studies were conducted according to OECD guidelines 423 and 407, respectively. Antinociceptive activity was evaluated using hot plate, tail flick, formalin-induced paw licking, and acetic acid-induced writhing models in rats. Mechanistic investigations were carried out using Nalbin, Atropine, Glibenclamide, and Terazosin to assess the involvement of opioidergic, cholinergic, KATP channel, and noradrenergic pathways respectively.
RESULTS: Phytochemical screening revealed the presence of phenolics, flavonoids, alkaloids, glycosides, tannins, saponins, amino acids, and reducing sugars. HPLC analysis identified chlorogenic acid, quercetin, gallic acid, syringic acid, vanillic acid, and coumaric acid derivatives. The extract exhibited considerable DPPH free radical scavenging activity with an IC50 value of 145.77 ± 4.30 μg/mL. In addition, the extract contained high levels of phenolic and flavonoid constituents, with total phenolic content of 98.35 ± 3.12 mg gallic acid equivalents (GAE)/g extract and total flavonoid content of 65.20 ± 2.45 mg catechin equivalents (CE)/g extract. Acute and subacute toxicity studies showed no mortality or significant toxicological alterations. CGEE produced significant (p < 0.05) dose-dependent mg/kg. Mechanistic studies demonstrated the involvement of opioidergic, cholinergic, ATP-sensitive K+ channel, and noradrenergic pathways.
CONCLUSION: The findings provide pharmacological evidence supporting the traditional use of C. gigantea in pain management. The antinociceptive effects may be associated with the synergistic action of phenolic and flavonoid constituents through modulation of multiple nociceptive pathways. CGEE also demonstrated a favorable safety profile, supporting its potential as a source of novel antinociceptive agents.
AIM OF THE STUDY: The present study aimed to evaluate the antinociceptive activity, safety profile, phytochemical composition, and possible mechanisms underlying the antinociceptive effects of the ethanolic extract of flowers of C. gigantea (CGEE).
MATERIALS AND METHODS: Phytochemical profiling was performed using qualitative screening, total phenolic and flavonoid assays, DPPH radical scavenging assay, and HPLC analysis. Acute and subacute oral toxicity studies were conducted according to OECD guidelines 423 and 407, respectively. Antinociceptive activity was evaluated using hot plate, tail flick, formalin-induced paw licking, and acetic acid-induced writhing models in rats. Mechanistic investigations were carried out using Nalbin, Atropine, Glibenclamide, and Terazosin to assess the involvement of opioidergic, cholinergic, KATP channel, and noradrenergic pathways respectively.
RESULTS: Phytochemical screening revealed the presence of phenolics, flavonoids, alkaloids, glycosides, tannins, saponins, amino acids, and reducing sugars. HPLC analysis identified chlorogenic acid, quercetin, gallic acid, syringic acid, vanillic acid, and coumaric acid derivatives. The extract exhibited considerable DPPH free radical scavenging activity with an IC50 value of 145.77 ± 4.30 μg/mL. In addition, the extract contained high levels of phenolic and flavonoid constituents, with total phenolic content of 98.35 ± 3.12 mg gallic acid equivalents (GAE)/g extract and total flavonoid content of 65.20 ± 2.45 mg catechin equivalents (CE)/g extract. Acute and subacute toxicity studies showed no mortality or significant toxicological alterations. CGEE produced significant (p < 0.05) dose-dependent mg/kg. Mechanistic studies demonstrated the involvement of opioidergic, cholinergic, ATP-sensitive K+ channel, and noradrenergic pathways.
CONCLUSION: The findings provide pharmacological evidence supporting the traditional use of C. gigantea in pain management. The antinociceptive effects may be associated with the synergistic action of phenolic and flavonoid constituents through modulation of multiple nociceptive pathways. CGEE also demonstrated a favorable safety profile, supporting its potential as a source of novel antinociceptive agents.