Sarcandra glabra (Thunb.) Nakai relieves pain behavior by inhibiting NaV1.7 channels

Ethnopharmacological relevance: Sarcandra glabra (Thunb.) Nakai has been traditionally utilized to alleviate pain, treat chronic bronchitis, and enhance immune function. Despite its wide-ranging applications in traditional medicine, detailed studies on its analgesic mechanisms remain limited.

Aim of the study: The objective was to evaluate the pain-relieving properties of raw extracts from S. glabra and understand the molecular mechanisms responsible for its pain relief benefits.

Materials and methods: By collecting S. glabra plant Materials from Yunnan Province and using ethanol extraction methods, the ethanol extract of S. glabra (ZJF) was prepared and evaluated for its anti-nociceptive activity using hot plate-induced and acetic acid-induced pain tests. Simultaneously, using HEK293T cells expressing the voltage-gated Sodium Channel subtype Na_V1.7, patch-clamp recordings were employed to study the inhibitory effects of ZJF on the Na_V1.7 channel and to screen for the key bioactive compound isofraxidin. Additionally, studies were conducted on the inhibitory characteristics of isofraxidin against the Na_V1.7 channel, and its in vivo anti-nociceptive activity was assessed in a mouse model.

Results: The crude extracts of S. glabra plant effectively mitigated pain sensation, showing robust analgesic activity in mice pain models induced by heat and acetic acid. Electrophysiological screening revealed that isofraxidin is the bioactive compound in S. glabra responsible for its analgesic properties. The current-voltage and conductance-voltage relationships of isofraxidin's inhibition of the Na_V1.7 channel suggest that isofraxidin directly binds to the pore region of the Na_V1.7 channel.

Conclusion: In preclinical evaluations, S. glabra and isofraxidin have demonstrated potential as effective anti-nociceptive agents. Their ability to alleviate pain is likely due to their inhibition of the Na_V1.7 channel, which is crucial for pain initiation, transmission, and regulation. These findings shed light on the molecular mechanisms behind the analgesic properties of S. glabra. Additionally, isofraxidin shows great potential in the creation of new pain-relief medications that target the Na_V1.7 channel.

Anti-nociceptive agents; Isofraxidin; Na(V)1.7 channel; Sarcandra glabra.