TABLE 4.
Therapeutic compounds that show promise in the prevention of IVDD and LBP
| Naturally occurring NP protective phytochemicals with an ability to inhibit IVDD | ||
|---|---|---|
| Gefitinib | Gefitinib, a tyrosine kinase inhibitor, suppresses EGFR and has protective properties against IVDD in the rat IVD. | 280 |
|
Atsttrin TNFα inhibitor of IVDD |
Atsttrin, an engineered protein identified from studies on progranulin, inhibits TNF‐α‐induced inflammation and suppresses IVDD. | 281 |
| SIRT1, Sirtuin family member NAD‐dependent deacetylase | SIRT1 has protective effects in a puncture‐induced IVDD model. Resveratrol, a SIRT1 activator also protects against puncture‐induced IVDD. | 282 |
|
Lycorine, alkaloid of lily family and daffodilsLycorine (Lycoris radiate) pyrrolophenanthridine |
Suppresses MMP‐3, 13, ADAMTS‐4, 5 expression by CEP cells through prevention of NFκB signaling and IL‐1β‐induced endplate degeneration. Reduces proinflammatory cytokines, suppresses expression of MMP‐3, 13, ADAMTS‐4, 5 by CEP cells via inhibition of NFκB signaling. | 283, 284 |
| Tanshinone IIA | Reduces inflammation and radiculopathic pain, inhibits IRAK‐1 and NF‐κB/p38/JNK signaling and pro‐inflammatory mediator production, MMP expression, and radiculopathic pain. | 285 |
| Icariin | Attenuates IL‐1β‐induced inflammatory response in human NP cells. | 286 |
| Wogonin | Inhibits IVDD through upregulation of Nrf2/ARE and MAPK signaling. | 287 |
| Epigallocatechin 3‐gallate | Suppresses IL‐1β‐induced inflammatory responses in IVD cells in vitro and reduces radiculopathic pain in‐vivo. | 288 |
| Quercetin | Inhibits apoptosis of NP cells, alleviates IVDD by modulating p38 MAPK‐mediated SIRT‐1 autophagy pathway and the Nrf2/NF‐κB axis. | 289, 290, 291 |
| Diosmin, citrus flavonoid | Trialed for treatment of LBP, reduces neuropathic pain in mice/rat models. | 292, 293, 294 |
| Procyanidin B3 dimer | Aleviates IVDD via interaction with the TLR4/MD‐2 complex. | 295 |
| Luteolin | Inhibits IL‐1β‐induced NP apoptosis /catabolism, ameliorates IVDD. | 296 |
| Baicalein | Inhibits IL‐1β‐induced inflammation in NP cells in‐vitro and IVDD. | 297 |
| Hesperidin | Anti‐hyperalgesic properties in a rat neuropathic pain model, has anti‐oxidant and anti‐inflammatory properties. | 298 |
| Curcumol | Alleviates inflammation in NP cells via PI3K/Akt/NF‐κB signaling. | 299 |
| Mangiferin | Alleviates NP mitochondrial ROS, suppresses NF‐κB signaling pathway. | 300 |
| Naringin, Naringenin | Protects human NP cells from TNF‐α‐induced inflammation, oxidative stress, enhanced AMPK/SIRT1 autophagy, IVD repair, reduces LBP. | 301, 302, 303 |
| Cannabidiol (CBD) | Alleviates pain via CB‐1, 2R, G protein serotonin R; TRPV‐1, PPAR, prevents anti‐oxidative stress, inflammation, senescent effects in NP. Suppresses MMP‐9, 13, induces Coll II, SOX‐9 via AMPK/GSK3β pathway. | 304, 305, 306, 307, 308, 309, 310, 311, 312, 313 |
| Celastrol pentacyclic quinone of T. wilfordii | Decreases MMP‐3, 9, 13, ADAMTS‐4, 5, COX‐2, iNOS, IL‐6 and TNF‐α in a rat IVDD model, inhibits the NF‐κB pathway in NP cells | 314 |
| Ligustilide (Ligustrazine) essential oil from Ligusticum striatum | Inhibits apoptosis, iNOS, COX‐2, TNF‐α/IL‐6 expression in NP cells, IVDD, suppresses aberrant TGFβ activation in NP cells, anti‐inflammatory, reduces IVDD and neurogenic pain. | 314, 315 |
| Ganoderic acid A, hetero‐ cyclic triterpenoid of Ganoderma lucidum fungi | Suppresses activation of TLR4/NLRP3 signaling, inhibits H2O2 induced apoptosis, inflammatory cytokines and oxidative stress, up‐regulates Col II and aggrecan production by NP cells. | 316 |
| Animal metabolites with pain relieving properties | ||
| Resolvin D1 (RvD1) | RvD1 is a pro‐resolving lipid mediator that reduces neuropathic pain. SC stimulation reduces CSF IL‐1β levels and increases RvD1 levels alleviating IL‐1β induced neuropathic pain and neuroinflammation. | 317, 318 |
| Hemorphins | Hemorphin LVV‐H7 has analgesic effects in a model of SC injury, through IL‐1 blockade by IL‐R antagonist protein and activation of opioid receptors. | 319 |
Abbreviations: Akt, serine/threonine‐specific protein kinase; AMPK, 5′ AMP‐activated protein kinase; CSF, cerebrospinal fluid; EGFR, epidermal growth factor receptor; GSK3β, Glycogen synthase kinase‐3 beta; IRAK‐1, interleukin‐1 receptor‐associated kinase‐1; JNK, c‐Jun N‐terminal kinase; NFκB, Nuclear factor kappa B; Nrf2, Nuclear factor erythroid 2‐related factor 2/ARE and MAPK, mitogen‐activated protein kinase; MD‐2, lymphocyte antigen 96; PI3K, phosphatidyl‐3 kinase; PPAR, peroxisome proliferator‐activated receptor; ROS, reactive oxygen species; SIRT‐1, NAD‐dependent deacetylase sirtuin‐1; SC, spinal cord; TLR4, Toll‐like receptor‐4; TRPV‐1, transient receptor potential cation channel subfamily V member 1.