New advances in Nrf2-mediated analgesic drugs. Phytomedicine : international journal of phytotherapy and phytopharmacology BACKGROUND:Oxidative stress is an inevitable process that occurs during life activities, and it can participate in the development of inflammation. Although great progress has been made according to research examining analgesic drugs and therapies, there remains a need to develop new analgesic drugs to fill certain gaps in both the experimental and clinical space. PURPOSE:This review reports the research and preclinical progress of this class of analgesics by summarizing known nuclear factor E-2-related factor-2 (Nrf2) pathway-modulating substances. STUDY DESIGN:We searched and reported experiments that intervene in the Nrf2 pathway and its various upstream and downstream molecules for analgesic therapy. METHODS:The medical literature database (PubMed) was searched for experimental studies examining the reduction of pain in animals through the Nrf2 pathway, the research methods were analyzed, and the pathways were classified and reported according to the pathway of these experimental interventions. RESULTS:Humans have identified a variety of substances that can fight pain by regulating the expression of Nrf2 and its upstream and downstream pathways. CONCLUSION:The Nrf2 pathway exerts anti-inflammatory activity by regulating oxidative stress, thereby playing a role in the fight against pain. 10.1016/j.phymed.2022.154598

The analgesic activities of total alkaloids of the ethnic medicine Cynanchum komarovii Al. Iljinski. Wang Ruizhou,Tao Li,Lu Qiang,Hao Fusheng,Zhao Shipeng,Ma Yan,Han Lu,Bai Changcai Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Cynanchum komarovii Al. Iljinski is a ethnomedicinal herb and this ethno-medicine is used mainly to treat arthritis, toothache, reducing phlegm, relieving cough. Total alkaloids of Cynanchum komarovii Al. Iljinski (TACKI) is the main active compound of Cynanchum komarovii Al. Iljinski. Previous investigations have revealed that TACKI can significantly inhibit rat foot swelling caused by carrageenan; it has a significant inhibitory effect on granulation tissue proliferation. Pharmacology study showed that Cynanchum komarovii Al. Iljinski has analgesia, anti-inflammatory, antibacterial, anti-tumor, relieving cough and relieving asthma. However, there is no any investigation on the mechanism of analgesia and anti-inflammation. AIM OF THE STUDY:To clarify the analgesic effect and material basis of Cynanchum komarovii Al. Iljinski, determine the analgesic effect of TACKI, and provide experimental data support for its traditional application in the treatment of various pains. MATERIALS AND METHODS:TACKI were prepared by the traditional acid extraction and alkaline precipitation method, and TACKI was analyzed through classic animal models of acute antinociceptive animal models and chronic antinociceptive. Evaluation of analgesic effects, and preliminary discussion of the mechanism of its analgesic effects were performed in this work. RESULTS:Acute toxicity experiments showed that the LD of TACKI mice was 2960.88 mg/kg, and symptoms of poisoning appeared. Patholog of liver and kidney studies have shown that TACKI reduces eosinophils and increases basophils in kidney glomeruli. In the study of analgesic effects, TACKI had analgesic activity through the PWL, formalin test, and acetic acid writhing test. In the chronic inflammatory antinociceptive study, the latency of the withdrawal reflex in the TACKI group was prolonged, and the mechanical withdrawal reflex threshold was significantly increased. The protein expression of NMDA, GFAP and Iba-1 in rat brain tissue can be reduced significantly byTACKI. Meanwhile, the content of TNF-α and IL-6 in rat brain tissue is reduced. CONCLUSION:TACKI has a significant analgesic activities. It may be related to inhibiting the activation of astrocytes and reducing the content of inflammatory mediators. 10.1016/j.jep.2021.114861