Wikstroemia indica (L.) C. A. Mey. Exerts analgesic activity by inhibiting Na_V1.7 channel

Wikstroemia indica (L.) C. A. Mey. is traditionally used for the treatment of gastrointestinal disorders, respiratory illnesses, skin infections, and inflammatory conditions. Despite extensive evidence of its biological potential, including antipyretic, antimicrobial, antifungal, anti-inflammatory, and diuretic properties, there are currently no reports indicating its analgesic effects.

Crude extracts from W. indica stems were examined for anti-nociceptive activity. Additionally, an in-depth investigation was conducted to uncover the molecular basis for the possible analgesic phenomenon.

W. indica stems were subjected to ethanol extraction. To evaluate the in vivo analgesic activity, both chemical and physical-induced pain models were employed. Additionally, single-cell electrophysiological recordings were performed on human embryonic kidney 293T (HEK293T) cells expressing Na_V1.7 channel.

Crude extracts derived from W. indica exhibited significant efficacy in mitigating the pain sensation, as evidenced by their substantial effects in both acetic acid-induced and heat-induced pain models. Further screening unveiled osthenol as a key bioactive compound responsible for mediating the analgesic properties of W. indica. Osthenol directly interacts with the pore domain of Na_V1.7 channels, leading to channel inhibition. Importantly, this interaction is independent of any changes in the channel gating modifier domain.

Both W. indica and osthenol demonstrate potential as effective anti-nociceptive agents in preclinical studies. Their analgesic effects are likely achieved by inhibiting the Na_V1.7 channel, which is crucial in pain initiation, transmission, and modulation. These results elucidate the molecular basis of the W. indica as a pain-relieving medication. Additionally, osthenol holds great potential in advancing the development of anti-nociceptive drugs targeting the Na_V1.7 channel.