Higenamine inhibits acute and chronic inflammatory pain through modulation of TRPV4 channels.

Pain is the cardinal symptom of many debilitating diseases and results in heavy health and economic burdens worldwide. Asarum (Asarum sieboldii Miq.) is a commonly used analgesic in Chinese medicine. However, the analgesic components and mechanisms of asarum in acute and chronic pain mice model remain unknown. In this study, we first generated asarum water extract and confirmed strong analgesic properties in mice in both the acute thermal and mechanical pain models, as well as in the complete Freund's adjuvant (CFA) induced chronic inflammatory pain model. Second, we identified higenamine as a major component of asarum and found that higenamine significantly inhibited thermal and mechanical induced acute pain and CFA induced chronic inflammatory pain. Then, using Trpv4-/- mice, we found that TRPV4 is necessary for CFA induced thermal and mechanical allodynia, and demonstrated that higenamine analgesia in the CFA model is partly through TRPV4 channel inhibition. Finally, we found that GSK1016790A, a TRPV4 agonist, induced calcium response was significantly inhibited by higenamine in both cultured DRG neurons and TRPV4 transfected HEK293 cells. Consistent with calcium imaging results, higenamine pretreatment also dose-dependently inhibited GSK1016790A induced acute pain. Taken together, our behavior and calcium imaging results demonstrate that the asarum component higenamine inhibits acute and chronic inflammatory pain by modulation of TRPV4 channels.

The effect of music intervention on sedation in elderly patients undergoing transurethral resection of prostate under spinal anesthesia: a prospective randomized controlled clinical trial.

PURPOSE: Music intervention is commonly used as a non-pharmacologic therapeutic modality to alleviate anxiety in perioperative patients. This study aimed to assess the sedative and anxiolytic effects of music on elderly patients receiving transurethral resection of prostate (TURP) under spinal anesthesia. METHODS: This was a prospective randomized controlled trial on patients who aged over 60 and received TURP under spinal anesthesia. Participants were randomized to the music group or the control group (no music). The primary outcome was perioperative BIS values, and the secondary outcomes were patient's perioperative anxiety levels, heart rate (HR), blood pressure, and patient satisfaction score. RESULTS: A total of 82 patients were analyzed. The perioperative BIS values in the music group were significantly lower than those of the control group at almost all time points (P < 0.001), as well as showed a significant reduction compared with baseline (P < 0.001), whereas the control group did not. In comparison with the control group, systolic blood pressure (SBP) significantly decreased in the music group at the beginning (mean difference, - 8.0 mmHg; 95% CI - 15.70 to 0.35; P = 0.041) and the 60th minute (mean difference, - 7.9 mmHg; 95% CI - 15.30 to 0.51; P = 0.037) of TURP. Furthermore, compared with baseline within the music group, diastolic blood pressure (DBP) and HR significant reduced at whole time points (P < 0.05), yet the control group not. CONCLUSION: Music intervention effectively provided slight sedation for elderly patients when undergoing TURP under spinal anesthesia without sedatives.

Percutaneous albumin/doxycycline injection versus open surgery for aneurysmal bone cysts in the mobile spine.

PURPOSE: This study aimed to validate the safety and effectiveness of percutaneous doxycycline/albumin injection for spinal aneurysmal bone cysts (ABCs) as an alternative to open surgery. METHODS: From January 2000 to December 2016, 25 patients who had no/minor neurological deficits (modified Frankel scale D or E) and acceptable local stability (spinal instability neoplastic score < 12) were included in the study, of whom 14 were treated with percutaneous doxycycline/albumin injection (injection group) and 11 were treated with open surgery (surgery group). The demographic and clinical information of the injection and surgery groups were recorded and compared. RESULTS: In the injection group, lesion size was significantly reduced in all 14 patients, all patients showed complete neurological recovery, and 13 patients had complete relief of neck pain; their mean visual analogue scale (VAS) decreased from 3.4 to 0.5. No complication or recurrence was observed during the mean 30.7-month follow-up (range, 24-50 months). In the surgery group, 9 patients had complete neurological recovery and 2 patients had residual slight paresthesia; their mean VAS decreased from 3.4 to 0.5. Two had local recurrence during their follow-up at 66.5 months (range, 50-96 months). Compared with the surgery group, the injection group showed no significant difference in the rate of recurrence (P = 0.14) and complication (P = 0.36). CONCLUSIONS: Percutaneous doxycycline/albumin injection for spinal ABCs can be safely and effectively performed in well-selected cases. It could serve as an alternative treatment, especially for spinal ABCs lesions with acceptable local stability and in patients without severe neurological deficits. These slides can be retrieved under Electronic Supplementary Material.

Osthole inhibits histamine-dependent itch via modulating TRPV1 activity.

Osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson, has long been used in China as an antipruritic herbal medicine; however, the antipruitic mechanism of osthole is unknown. We studied the molecular mechanism of osthole in histamine-dependent itch by behavioral test, Ca(2+) imaging, and electrophysiological experiments. First, osthole clearly remitted the scratching behaviors of mice induced with histamine, HTMT, and VUF8430. Second, in cultured dorsal root ganglion (DRG) neurons, osthole showed a dose-dependent inhibitory effect to histamine. On the same neurons, osthole also decreased the response to capsaicin and histamine. In further tests, the capsaicin-induced inward currents were inhibited by osthole. These results revealed that osthole inhibited histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how osthole exerts anti-pruritus effects and suggests that osthole may be a useful treatment medicine for histamine-dependent itch.

[Relationship between artesunate influence on the process of TGF-beta1 induced alveolar epithelial cells transform into mesenchymal cells and on idiopathic pulmonary fibrosis].

This study is to investigate the effect of artesunate on transforming growth factor-beta1 (TGF-beta1) induced epithelial-mesenchymal transition (EMT) and its possible mechanism. After the in vitro cultured RLE-6TN cells were treated with TGF-beta1 then artesunate intervened on it, after 24 h, expression of the markers of mesenchymal cell was assayed using Western blotting and real-time PCR analysis. Western blotting was also used to detect the effect of TGF-beta1 on the Smad3 and Smad7 expressions of RLE-6TN cells. Morphological alterations were examined by phase-contrast microscope, and ultrastructure changes by electron microscope. Incubation of RLE-6TN cells with TGF-beta1 resulted in the up-regulation of the expression of the mesenchymal cell markers, after artesunate intervened on it, resulted in the down-regulation of the expression. Meanwhile, incubation with artesunate intervened on RLE-6TN cells could lead to the apparent down-regulation of the expression of Smad3 and up-regulation of Samd7 and the transition of RLE-6TN cells to mesenchymal-like by TGF-beta1 induction, after artesunate intervened on it, RLE-6TN cells to epithelial-like. TGF-beta1 induced epithelial-mesenchymal transition process; artesunate can inhibit TGF-beta1-induced epithelial-mesenchymal transition process, the possible mechanism is up-regulation of the expression of Smad7 and down-regulation of the expression of Smad3, meanwhile inhibits phosphorylation of Smad3.

Synergism and rules from combination of Baicalin, Jasminoidin and Desoxycholic acid in refined Qing Kai Ling for treat ischemic stroke mice model.

Refined Qing-Kai-Ling (QKL), a modified Chinese medicine, consists of three main ingredients (Baicalin, Jasminoidin and Desoxycholic acid), plays a synergistic effect on the treatment of the acute stage of ischemic stroke. However, the rules of the combination and synergism are still unknown. Based on the ischemic stroke mice model, all different kinds of combination of Baicalin, Jasminoidin, and Desoxycholic acid were investigated by the methods of neurological examination, microarray, and genomics analysis. As a result, it confirmed that the combination of three drugs offered a better therapeutical effect on ischemic stroke than monotherapy of each drug. Additionally, we used Ingenuity pathway Analysis (IPA) and principal component analysis (PCA) to extract the dominant information of expression changes in 373 ischemia-related genes. The results suggested that 5 principal components (PC1-5) could account for more than 95% energy in the gene data. Moreover, 3 clusters (PC1, PC2+PC5, and PC3+PC4) were addressed with cluster analysis. Furthermore, we matched PCs on the drug-target networks, the findings demonstrated that Baicalin related with PC1 that played the leading role in the combination; Jasminoidin related with PC2+PC5 that played a compensatory role; while Desoxycholic acid had the least performance alone which could relate with PC3+PC4 that played a compatible role. These manifestations were accorded with the principle of herbal formulae of Traditional Chinese Medicine (TCM), emperor-minister-adjuvant-courier. In conclusion, we firstly provided scientific evidence to the classic theory of TCM formulae, an initiating holistic viewpoint of combination therapy of TCM. This study also illustrated that PCA might be an applicable method to analyze the complicated data of drug combination.

Cerebrosides of baifuzi, a novel potential blocker of calcium-activated chloride channels in rat pulmonary artery smooth muscle cells.

Calcium-activated chloride channels (CaCCs) are crucial regulators of vascular tone by promoting a depolarizing influence on the resting membrane potential of vascular smooth muscle cells. However, the lack of a special blocker of CaCCs has limited the investigation of its functions for long time. Here, we report that CB is a novel potential blocker of I(Cl(Ca)) in rat pulmonary artery smooth muscle cells (PASMC). Cerebrosides (CB) were isolated from Baifuzi which is dried root tuber of the herb Typhonium giganteum Engl used for treatment of stroke in traditional medicine. Using the voltage-clamp technique, sustained Ca(2+)-activated Cl(-) current (I(Cl(Ca))) was evoked by a K(+)-free pipette solution containing 500nM Ca(2+) which exhibited typical outwardly rectifying and voltage-/time-dependence characterization. Data showed that CB played a distinct inhibitory role in modulating the CaCCs. Moreover, we investigated the kinetic effect of CB on I(Cl(Ca)) and found that it could slow the activation dynamics of the outward current, accelerate the decay of the inward tail current and change the time-dependence characterization. We conclude that CB is a novel potent blocker of CaCCs. The interaction between CB and CaCCs is discussed.

[Experimental study on the effect of ginkgo bioba extract on the expression of heme oxygenase-1 in bronchial asthma].

AIM: To explore the effect of the ginkgo bioba extract on the expression of heme oxygenase-1 (HO-1) in bronchial asthma. METHODS: 30 guinea pigs were randomly divided into 3 groups (n = 10): (1) Normal control group; (2) Asthmatic group; (3) Therapeutic group. Blood carbon monoxide Hb (COHb) percent value, Airway resistance and eosinophilic inflammation of airway wall were observed, the expression of HO-1 in lung tissue were observed by immunohistochemical staining. RESULTS: The expression of HO-1 was mainly located in airway epithelium in these 3 groups, the optical densities were 0.170 +/- 0.020, 0.707 +/- 0.058, 0.397 +/- 0.034, respectively. The asthmatic group showed higher optical densities than that of the normal control group (P < 0.01), and the therapeutic group showed lower optical density than asthmatic group (P < 0.01). CONCLUSION: The expression of HO-1 is inhibited significantly by the treatment of the ginkgo bioba extract, which may be one of the mechanism for treating asthma by ginkgo bioba extract.