Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury-associated peripheral sensory neuropathy via block of N- and T-type calcium channels

Pain
Shreya S BellampalliRajesh Khanna

Abstract

The Federal Pain Research Strategy recommended development of nonopioid analgesics as a top priority in its strategic plan to address the significant public health crisis and individual burden of chronic pain faced by >100 million Americans. Motivated by this challenge, a natural product extracts library was screened and identified a plant extract that targets activity of voltage-gated calcium channels. This profile is of interest as a potential treatment for neuropathic pain. The active extract derived from the desert lavender plant native to southwestern United States, when subjected to bioassay-guided fractionation, afforded 3 compounds identified as pentacyclic triterpenoids, betulinic acid (BA), oleanolic acid, and ursolic acid. Betulinic acid inhibited depolarization-evoked calcium influx in dorsal root ganglion (DRG) neurons predominantly through targeting low-voltage-gated (Cav3 or T-type) and CaV2.2 (N-type) calcium channels. Voltage-clamp electrophysiology experiments revealed a reduction of Ca, but not Na, currents in sensory neurons after BA exposure. Betulinic acid inhibited spontaneous excitatory postsynaptic currents and depolarization-evoked release of calcitonin gene-related peptide from lumbar spinal cord slic...Continue Reading

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Citations

May 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexsander Rodrigues Carvalho JuniorLuís Cláudio Nascimento da Silva
Sep 4, 2019·Current Treatment Options in Neurology·Vanessa BauteFatemeh Sadeghifar
Jan 24, 2020·Frontiers in Molecular Neuroscience·Elizabeth Martínez-HernándezErika S Piedras-Rentería
May 1, 2020·British Journal of Pharmacology·Robson da CostaJoão B Calixto
Jan 11, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Song CaiRajesh Khanna
Jan 10, 2021·Redox Biology·Ildiko SzaboLucia Biasutto
Dec 22, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Ho-Sung LeeDae-Yeon Lee

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