Senkyunolide I Relieves Neuropathic Pain Induced by Chronic Constriction Injury by Inhibiting Activation of Microglia

As an alternative to the use of narcotics, generally refractory to long-term effectiveness, for the management of neuropathic pain, we have explored the utility of senkyunolide I. Senkyunolide I is one of the bioactive components isolated from Ligusticum chuanxiong Hort known to exhibit multiple biological activities. In this study, we report senkyunolide I inhibition of chronic constriction injury induced neuropathic pain. Mechanistically, senkyunolide I inhibited chronic constriction injury induced apoptosis and the activity of microglia via extracellular signal regulated kinase pathway. We therefore suggest that senkyunolide I could serve as a promising drug for the treatment of neuropathic pain.

Senkyunolide I Protects against Sepsis-Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis-associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6, and IL-1β. A fear conditioning test was performed, and the results showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, and p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in the hippocampus homogenate. Sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.

Synergistic Effects of Cryptotanshinone and Senkyunolide I in Guanxinning Tablet Against Endogenous Thrombus Formation in Zebrafish

Thrombosis is a key pathological event in cardiovascular diseases, and is also the most important targeting process for their clinical management. New drug development in thrombosis treatment is still in great demand. According to the traditional Chinese medicine (TCM) theory, thrombosis belongs to the syndrome of blood stasis. Salvia miltiorrhiza Bunge and Ligusticum striatum DC. are two common TCM herbs with long-term documented function in promoting blood circulation and inhibiting thrombosis, especially when used together. Guanxinning Tablet, a modern Chinese drug which contains extracts of the two herbs, also showed strong therapeutic effects in coronary heart disease. However, the pharmacological mechanism is still lacking for the compatibility of the two herbs. Here, through zebrafish-based in vivo fluorescence screening, we demonstrated the synergistic effects between S. miltiorrhiza Bunge and L. striatum DC. in regulating endogenous thrombosis. Moreover, combined with high-resolution mass spectrometry, the main compounds of the botanical drugs were analyzed and screened in our model system. Interestingly, cryptotanshinone and senkyunolide I, two representative compounds, respectively derived from the two herbs, also showed synergistic antithrombotic effects. Further analysis suggested that they may regulate thrombi formation at different levels via multiple signaling pathways, including oxidative stress, platelet activation and coagulation cascade. Taken together, our findings provided solid biological supports toward the drug compatibility theory of TCM, and suggested cryptotanshinone and senkyunolide I as promising drug candidates in thrombosis management.

Senkyunolide I Protects Against Sepsis-associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

Background: Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide sedative effect to improve sleep. But its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP).Methods: The male C57BL/6 mice were used to investigate the effects of Senkyunolide I on SAE. The related protein of the sleep deprivation and inflammatory signaling pathway was detected by western blot. The activation of microglia and the neuronal apoptosis were separately detected by immunofluorescence staining and TUNEL staining.Results: Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6 and IL-1β. A fear conditioning test was performed and the result showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6 and IL-1β, in the hippocampus homogenate. The sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Conclusion: Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.

Simultaneous Determination of Night Effective Constituents and Correlation Analysis of Multiconstituents and Antiplatelet Aggregation Bioactivity In Vitro in Chuanxiong Rhizoma Subjected to Different Decoction Times

Several effective constituents, such as vanillin, ferulic acid, senkyunolide I, senkyunolide H, coniferyl ferulate, Z-ligustilide, butylphthalide, senkyunolide A, and levistilide A, are unstable and possess mutual transformation relationships in Chuanxiong Rhizoma (CR). Traditional Chinese medicine mainly involves decoction, and the content of effective constituents and antiplatelet aggregation bioactivity (AAB) in CR may vary with different decoction time (10 min, 20 min, 30 min, 40 min, 50 min, and 60 min). Here, we showed that coniferyl ferulate and levistilide A were detected in CR material, but not in the decoction. The effective components possessed transformation and degradation in CR decoction of different times. The effective components and the strength of AAB at 10 and 20 minutes were the strongest, followed by 30–50 minutes, and 60 minutes were the weakest by analysis of SIMCA-PLS in CR decoction of different times. In the Pearson correlation analysis, there were correlations (P<0.05) between effective components, which were ferulic acid and senkyunolide I (coefficient was 0.976), ferulic acid and senkyunolide H (coefficient was 0.972), senkyunolide I and senkyunolide H (coefficient was 0.982), senkyunolide A and butylphthalide (coefficient was 0.974), senkyunolide A and Z-ligustilide (coefficient was 0.947), and butylphthalide and Z-ligustilide (coefficient was 0.993). Effective components (ferulic acid, senkyunolide I, and senkyunolide H) and AAB were correlated and the Pearson correlation coefficients were respectively 0.965, 0.973, and 0.999. In the stepwise regression analysis, senkyunolide H and senkyunolide I were correlated with AAB (P<0.05). Senkyunolide H (H) was positively correlated with AAB, senkyunolide I (I) was negatively correlated with AAB, and its expression was AAB = 1.187 ∗ H − 0.199 ∗ I − 0.422. These findings indicate that there are some correlations between effective components and AAB in CR.

Identification of Chemical Markers for the Discrimination of Radix Angelica sinensis Grown in Geoherb and Non-Geoherb Regions Using UHPLC-QTOF-MS/MS Based Metabolomics

This research aimed to discover chemical markers for discriminating radix Angelica sinensis (RAS) from different regions and to explore the differences of RAS in the content of four active compounds and anti-inflammatory activities on lipopolysacchride (LPS)-induced RAW264.7 cells and calcium antagonists on the HEK 293T cells of RAS. Nine compounds were selected as characteristic chemical markers by ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS), based on metabolomics, in order to rapidly discriminate RAS from geoherb and non-geoherb regions. The contents of senkyunolide I and butylidenephthalide in geoherb samples were higher than those in non-geoherb samples, but the contents of ferulic acid and levistolide A were lower in the geoherb samples. Furthermore, the geoherbs showed better nitric oxide (NO) inhibitory and calcium antagonistic activities than the non-geoherbs. These results demonstrate the diversity in quality of RAS between geoherbs and non-geoherbs.