Analgesic Alkaloids Derived From Traditional Chinese Medicine in Pain Management

Abstract

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine, sinomenine, ligustrazine, evodiamine, brucine, tetrandrine, Stopholidine, and lappaconitine, focusing on their mechanisms and potential clinical applications. To better describe the mechanism of these alkaloids, we adopted the concept of drug-cloud (dCloud) theory. dCloud illustrated the full therapeutic spectrum of multitarget analgesics with two dimensions, which are “direct efficacy”, including inhibition of ion channels, activating γ-Aminobutyric Acid/opioid receptors, to suppress pain signal directly; and “background efficacy”, including reducing neuronal inflammation/oxidative stress, inhibition of glial cell activation, restoring the balance between excitatory and inhibitory neurotransmission, to cure the root causes of chronic pain. Empirical evidence showed drug combination is beneficial to 30–50% chronic pain patients. To promote the discovery of effective analgesic combinations, we introduced an ancient Chinese therapeutic regimen that combines herbal drugs with “Jun”, “Chen”, “Zuo”, and “Shi” properties. In dCloud, “Jun” drug acts directly on the major symptom of the disease; “Chen” drug generates major background effects; “Zuo” drug has salutary and supportive functions; and “Shi” drug facilitates drug delivery to the targeted tissue. Subsequently, using this concept, we interpreted the therapeutic effect of established analgesic compositions containing TCM derived analgesic alkaloids, which may contribute to the establishment of an alternative drug discovery model.

Efficacy and safety of TCMs with anti-inflammatory effect in patients with rheumatoid arthritis: A network meta-analysis

“…Sinomenine (SIN) is extracted from CAULIS SINOMENII, which is the main active ingredient of Zhengqing Fengtongning capsule ( 90 ). Many studies demonstrated sinomenine could alleviate morning stiffness and joint pain in the RA patients, by modifying neurotransmission, inhibiting cyclooxygenase 2-dependent prostaglandin E2 and NO, TNF, INF-γ, IL-6, IL-1β, and IL-4, and suppressing the activity of P38 MAPK, MMPs, and NF-κB ( 91 , 92 ). At the same time, SIN could regulate immunity and alleviate inflammation by inhibiting T- lymphocyte and B-lymphocyte activation ( 93 ), regulating NLRP3 inflammasome and NF-κB pathway ( 94 ).…”

Topical Traditional Chinese Medicines for Cancer Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“…There has been considerable research into the analgesic effects of compounds, notably alkaloids, contained in CHMs. 64 The included studies often tested multi-ingredient formulations, each of which contained multiple compounds, so it was not possible to determine which, if any, contributed to the clinical effect. In addition, the studies of multi-ingredient topical formulations generally did not provide the rationale for including each ingredient, so we cannot be certain that they were intended to exert anti-nociceptive effects.…”

Screening and identification of high yield tetramethylpyrazine strains in Nongxiangxing liquor Daqu and study on the mechanism of tetramethylpyrazine production

“…5 In addition, TTMP is also an important active component of Chuanxiong rhizome (Szechuan Lovage Rhizome), and it can be applied to the treatment of cardiovascular and cerebrovascular diseases. 6 Further, it has favorable curative effects on ischemic cardiovascular and cerebrovascular diseases in clinical practice. 7 According to some studies, TTMP in Baijiu can dilate blood vessels, improve microcirculation, and inhibit platelet aggregation.…”

“…It is a nitrogen‐containing heterocyclic compound characterized by a roasting and sweet aroma, and one of the important aroma compounds in Baijiu 5 . In addition, TTMP is also an important active component of Chuanxiong rhizome ( Szechuan Lovage Rhizome ), and it can be applied to the treatment of cardiovascular and cerebrovascular diseases 6 . Further, it has favorable curative effects on ischemic cardiovascular and cerebrovascular diseases in clinical practice 7 .…”