干旱区生态环境知识资源中心(Arid): 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

Arid

DOI	10.1097/j.pain.0000000000001385
	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
	Bellampalli, Shreya S.1; Ji, Yingshi 1,2; Moutal, Aubin 1; Cai, Song 1; Wijeratne, E. M. Kithsiri 3; Gandini, Maria A.4; Yu, Jie 1; Chefdeville, Aude 1; Dorame, Angie 1; Chew, Lindsey A.1; Madura, Cynthia L.1; Luo, Shizhen 1; Molnar, Gabriella 1; Khanna, May 1,5; Streicher, John M.1; Zamponi, Gerald W.4; Gunatilaka, A. A. Leslie 3; Khanna, Rajesh 1,5,6
通讯作者	Khanna, Rajesh
来源期刊	PAIN
ISSN	0304-3959
EISSN	1872-6623
出版年	2019
卷号	160 期号:1 页码:117-135
英文摘要	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 vottage-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 Ca2+, 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 slices. Notably, BA did not engage human mu, delta, or kappa opioid receptors. Intrathecal administration of BA reversed mechanical allodynia in rat models of chemotherapy-induced peripheral neuropathy and HIV-associated peripheral sensory neuropathy as well as a mouse model of partial sciatic nerve ligation without effects on locomotion. The broad-spectrum biological and medicinal properties reported, including anti-HIV and anticancer activities of BA and its derivatives, position this plant-derived small molecule natural product as a potential nonopioid therapy for management of chronic pain.
英文关键词	Desert lavender extract Betulinic acid T-type calcium channels Cav3.2/3.3 Nonopioid HIV-induced sensory neuropathy Paclitaxel-induced peripheral neuropathy
类型	Article
语种	英语
国家	USA ; Peoples R China ; Canada
开放获取类型	Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000462391500015
WOS关键词	CA2+ CHANNELS ; CONSTELLATION PHARMACOLOGY ; TACTILE ALLODYNIA ; NATURAL-PRODUCTS ; CHRONIC PAIN ; DORSAL-ROOT ; NEURONS ; DERIVATIVES ; CA(V)3.2 ; EXPRESSION
WOS类目	Anesthesiology ; Clinical Neurology ; Neurosciences
WOS研究方向	Anesthesiology ; Neurosciences & Neurology
来源机构	University of Arizona
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/217834
作者单位	1.Univ Arizona, Coll Med, Dept Pharmacol, 1501 North Campbell Dr,POB 245050, Tucson, AZ 85724 USA; 2.Jilin Univ, Coll Basic Med Sci, Dept Pharmacol, Changchun, Jilin, Peoples R China; 3.Univ Arizona, Coll Agr & Life Sci, Nat Prod Ctr, Sch Nat Resources & Environm, Tucson, AZ 85724 USA; 4.Univ Calgary, Cumming Sch Med, Dept Physiol & Pharmacol, Calgary, AB, Canada; 5.Univ Arizona Hlth Sci, Ctr Innovat Brain Sci, Tucson, AZ USA; 6.Univ Arizona, Coll Med, Grad Interdisciplinary Program, Dept Neurosci, Tucson, AZ 85724 USA
推荐引用方式 GB/T 7714	Bellampalli, Shreya S.,Ji, Yingshi,Moutal, Aubin,et al. 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[J]. University of Arizona,2019,160(1):117-135.
APA	Bellampalli, Shreya S..,Ji, Yingshi.,Moutal, Aubin.,Cai, Song.,Wijeratne, E. M. Kithsiri.,...&Khanna, Rajesh.(2019).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,160(1),117-135.
MLA	Bellampalli, Shreya S.,et al."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 160.1(2019):117-135.