icaritin and Inflammation

Inflammatory pain is a chronic, persistent and serious disease that greatly impacts public health, which is often accompanied by allodynia, hyperalgesia, and spontaneous pain. It is evident that α7 nicotinic acetylcholine receptor (α7nAChR) plays a key role in cholinergic anti-inflammatory pathway and exhibits the inhibition of neuroinflammation in chronic pain. Trifluoro-icaritin (ICTF), a derivative of icaritin from the extract of a genus of Epimedium plant, is identified to possess profound anti-inflammatory activity. However, whether ICTF has anti-nociceptive effect on inflammatory pain and its potential mechanisms remain poorly elucidated. Intraperitoneal injection (i.p.) of ICTF to complete Freund's adjuvant (CFA)-induced inflammatory pain rats once daily for 21 consecutive days. Pain-related behaviors were evaluated with paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis. Expression of pain-related signaling molecules in the spinal cord were detected using qRT-PCR, western blot assay, and immunofluorescence staining. This results showed that ICTF (3.0 mg/kg, i.p.) effectively alleviated mechanical allodynia and thermal hyperalgesia not 0.3 and 1.0 mg/kg in CFA rats. Subsequently, we further observed that ICTF (3.0 mg/kg) dramatically decreased the mRNA and protein levels of HMGB1, NF-κB p65, and IL-1β but markedly enhanced α7nAChR and IL-10 expression in the spinal cord of CFA rats, and Immunofluorescence staining also showed that ICTF (3.0 mg/kg) significantly increased the expression of α7nAChR and reduced IBA1 in the spinal cord of CFA rats, along with suppressing the alterations of gait parameters induced by CFA. Moreover, Intrathecal injection (i.t.) of α7nAChR antagonist alpha-bungarotoxin (α-Bgtx, 1.0 μg/kg) not only reversed the anti-nociceptive effect of ICTF on pain hypersensitivity, but also inhibited the down-regulation of HMGB1, NF-κB p65, and IL-1β as well as the up-regulation of α7nAChR and IL-10 protein expression induced by ICTF treatment. Altogether, our results illustrate that ICTF enables to ameliorate CFA-induced inflammatory pain through α7nAChR-mediated inhibition of HMGB1/NF-κB signaling pathway in the spinal cord of rats, suggesting that ICTF may be exploited as a potential painkiller against chronic inflammatory pain.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Chronic Pain; Flavonoids; HMGB1 Protein; Hyperalgesia; Inflammation; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord

Inflammation and insomnia are medical problems that may severely affect work and health, thereby necessitating strategies for their effective treatment. Icartin (ICT) is a major active monomeric component of icariin  . Studies have revealed that ICT possesses several pharmacological properties such anti-inflammatory, anti-tumor, anti-fibrotic, anti-osteoporotic and neuroprotective effects. The present research was carried out to investigate the anti-inflammatory, analgesic and sedative/hypnotic effects of ICT. The results obtained revealed that ICT exerted a good anti-inflammatory effect related to the downregulations of inflammatory cytokines and the inhibition of COX-2 signaling pathway. Moreover, ICT enhanced Cl- influx in mouse cortical cells in a concentration-dependent manner. These data suggest that ICT exerts a hypnotic effect in mice through a mechanism associated with increased Cl- influx in cortical cells.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Brain; Chlorides; Cyclooxygenase 2; Ear; Female; Flavonoids; Hypnotics and Sedatives; Inflammation; Male; Mice; Pentobarbital; Signal Transduction; Sleep; Sleep Latency; Xylenes

Inflammation is a defensive response of the body and is at the center of many diseases' process like depression. High mobility group protein box 1 (HMGB1), has been proved to function as a pro-inflammatory cytokine. We aim to explore the role of HMGB1 played in the neuroinflammation here. In this study, we used LPS to induce an acute inflammatory response, and to measure the anti-neuroinflammation effect of icariin (ICA) and icaritin (ICT). We found that LPS could increase the expression of HMGB1 in serum and hippocampus, along with a high expression of HMGB1 in the cytoplasm and a high expression of RAGE, which could be rescued by ICA and ICT, and ethyl pyruvate (EP) pretreatment showed similar effects here. We speculated that the translocation of HMGB1 from the nucleus to the cytoplasm played an important role in neuroinflammatory process, and HMGB1-RAGE signal was involved in this process. Furthermore, we found that ICA and ICT treatment activated TLR4-XBP1s related NF-κB signal, which we thought was relevant with the neuroprotective effect of ICA and ICT. However, EP pretreatment suppressed TLR4-XBP1s- endoplasmic reticulum stress related NF-κB signal to anti-inflammatory response, which was almost absolutely opposite with ICA and ICT treatment. We speculated that it might be caused by the duration of inflammation. We supposed that ICA and ICT could ameliorate neuroinflammation in hippocampus via suppressing HMGB1-RAGE signaling and might show a neuroprotective effect via activating TLR4-XBP1s related NF-κB signal at the same time, making it possible to act as an anti-neuroinflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Flavonoids; Hippocampus; HMGB1 Protein; Inflammation; Interleukin-10; Lipopolysaccharides; Male; Mice, Inbred C57BL; Neuroprotective Agents; Receptor for Advanced Glycation End Products; Tumor Necrosis Factor-alpha

We aimed to investigate whether icaritin (ICT) would inhibit serum proinflammatory cytokines and postpone prostate cancer (PCa) development and progression in both normal diet and high-fat diet (HFD) transgenic adenocarcinoma mouse prostate (TRAMP) mice.. TRAMP mice were randomly divided into four groups: normal diet with/without ICT group and HFD with/without ICT group. Each TRAMP mouse received intraperitoneal injection of ICT solution at the dose of 30 mg/kg 5 times per week.. ICT treatment could significantly increase the survival when compared with those in normal diet group (P = 0.015, log-rank test) and HFD group (P = 0.009, log-rank test). Proinflammatory cytokine levels, including IL-1α, IL-1β, IL-6, and TNF-α, were decreased more or less in ICT-treated TRAMP mice. Moreover, significant higher inflammation scores were detected in normal diet group and HFD group compared with their relevant ICT treatment groups (P = 0.026 and P = 0.006, respectively). Meanwhile, the incidences of well-differentiated tumor tissue in two ICT treatment groups (39.13 and 31.82 %) were moderately higher than control groups (29.41 and 20.00 %, respectively), though no significant difference was observed.. Taken together, our findings indicate that ICT could inhibit the development and progression of PCa in TRAMP mice via inhibiting proinflammatory cytokines.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cytokines; Diet, High-Fat; Disease Models, Animal; Disease Progression; Flavonoids; Inflammation; Male; Mice; Mice, Transgenic; Prostatic Neoplasms; Signal Transduction