Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment.

Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.

Combined treatment of human mesenchymal stem cells and green tea extract on retinal ganglion cell regeneration in rats after optic nerve injury.

Retinal ganglion cell (RGC) death and axonal loss cause irreversible vision loss upon optic nerve (ON) injury. We have independently demonstrated that mesenchymal stem cells (MSCs) and green tea extract (GTE) promote RGC survival and axonal regeneration in rats with ON injury. Here we aimed to evaluate the combined treatment effect of human bone marrow-derived MSCs (hBM-MSCs) and GTE on RGC survival and axonal regeneration after ON injury. Combined treatment of hBM-MSCs and GTE promoted RGC survival and neurite outgrowth/axonal regeneration in ex vivo retinal explant culture and in rats after ON injury. GTE increased Stat3 activation in the retina after combined treatment, and enhanced brain-derived neurotrophic factor secretion from hBM-MSCs. Treatment of 10 µg/mL GTE would not induce hBM-MSC apoptosis, but inhibited their proliferation, migration, and adipogenic and osteogenic differentiation in vitro with reducing matrix metalloproteinase secretions. In summary, this study revealed that GTE can enhance RGC protective effect of hBM-MSCs, suggesting that stem cell priming could be a prospective strategy enhancing the properties of stem cells for ON injury treatment.

Seventeen undescribed iridoid derivatives with anti-inflammatory effects from Hedyotis diffusa and their structure-activity relationships.

Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC50 values of 5.69, 6.16, and 6.84 µM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents.

Du-Moxibustion in a Mouse Model of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a progressively worsening and disabling form of arthritis that primarily affects the axial skeleton. This disease mainly involves the spine and the sacroiliac joint. Fusion of the spine and the sacroiliac joint may occur in the later stage of the disease, resulting in spinal stiffness and kyphosis, as well as difficulty in walking, which seriously affects the quality of work and daily living activities and imposes a heavy burden on the patient, the family, and society. Increasing attention has been paid to non-pharmacotherapy as an alternative therapy for AS. Moxibustion is an ancient therapeutic technique used in Traditional Chinese Medicine (TCM). Du-moxibustion therapy, a unique and innovative external treatment developed on the basis of ordinary moxibustion, has a definite therapeutic effect on AS. Du-moxibustion skillfully combines the compatible techniques of TCM to integrate meridians, acupoints, Chinese herbal medicine, and moxibustion. This paper describes the operation procedures and precautions to be taken during Du-moxibustion in experimental mice in detail to provide an experimental basis for the study of the mechanism of Du-moxibustion in the treatment of AS.

Treatment with a flow diverter-assisted coil embolization for ruptured blood blister-like aneurysms of the internal carotid artery: a technical note and analysis of single-center experience with pooled data.

Treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) with flow diverters (FDs) has become widespread in recent years. However, ruptured blood blister-like aneurysm (BBA) of ICA treatment with flow diverter-assisted coil embolization (FDAC) remains controversial. Moreover, limited direct comparative studies have been conducted between the two treatment modalities, FDs and FDAC, for BBAs. The purpose of this study was to document our experience and evaluate the effectiveness and safety of FDAC. We conducted a retrospective analysis of clinical and radiological information from ten patients who experienced ruptured BBAs of the supraclinoid ICA at our center from January 2021 to February 2023. The technical details of FDAC for ruptured BBAs were described, and the technical steps were named "pipeline embolization device (PED)-Individualized shaping(microcatheter)-Semi deploying-Rivet(coils)-Massage(microwire)" as the PEISSERM technique. Clinical outcomes were assessed using the modified Rankin Scale (mRS), whereas radiological results were determined through angiography. A pooled analysis was implemented, incorporating data from literature sources that reported perioperative and long-term clinical and angiographic outcomes of ruptured BBAs treated with FD and FDAC strategies, along with our data. Data in our analysis pool were categorized into FD and FDAC strategy groups to explore the preferred treatment modalities for BBAs. The PEISSERM technique was utilized to treat ten patients, seven males, and three females, with an average age of 41.7 years. A single PED was deployed in conjunction with coils in all ten patients. All PEDs were documented to have good wall apposition. The immediate postoperative angiograms demonstrated Raymond grade I in ten aneurysms. Angiographic follow-up of nine patients at 4-25 months showed total occlusion of the aneurysms. At the most recent follow-up, the mRS scores of nine patients hinted at a good prognosis. Pooled analysis of 233 ICA-BBA cases of FD revealed a technical success rate of 91% [95% confidence interval (CI), 0.88 to 0.95], a rate of complete occlusion of 79% (95% CI, 0.73 to 0.84), a recurrence rate of 2% (95% CI, 0.00 to 0.04), a rebleed rate of 2% (95% CI, 0.00 to 0.04), and the perioperative stroke rate was 8% (95% CI, 0.04 to 0.11). The perioperative mortality was 4% (95% CI, 0.01 to 0.07). The long-term good clinical outcome rate was 85% (95% CI, 0.80 to 0.90). The mortality rate was 6% (95% CI, 0.03 to 0.09). Results from the subgroup analysis illustrated that the FDAC strategy for BBAs had a significantly higher immediate postoperative complete occlusion rate (P < 0.001), total occlusion rate (P = 0.016), and a good outcome rate (P = 0.041) compared with the FD strategy. The FDAC strategy can yield a higher rate of good outcomes than the FD strategy. The PEISSERM technique employed by the FDAC is a reliable and effective treatment approach as it can minimize the hemodynamic burden of BBA's fragile dome, thereby achieving an excellent occlusion rate. The PEISSERM technique in the FDAC strategy contributes to understanding the BBA's treatment and offers a potentially optimal treatment for BBA.

Six undescribed lavandulylated flavonoids with PTP1B inhibition from the roots of Sophora flavescens.

Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC50 values of 2.669 and 3.596 µM, respectively.

Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice.

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.

Green tea extract enhances retinal ganglion cell survival and axonal regeneration in rats with optic nerve injury.

Current clinical treatments have not yet effectively cured progressive retinal ganglion cell (RGC) death and axonal degeneration after optic nerve (ON) injury. We previously demonstrated green tea extract (GTE) can reduce RGC death in rats after ischemic injury. Here, we aim to determine the prophylactic and therapeutic effects and mechanisms of GTE on RGC survival and axonal regeneration in rats with ON injury. GTE (275 or 550 mg/kg) was administered intragastrically for 7 d before or 14 d post-ON crush surgery in adult Fischer 344 rats. Rats with pre- or post-operative treatment of 275 mg/kg GTE showed significantly higher numbers of RGCs and regenerated axons post-ON injury with improved pupillary light reflex as compared to saline-treated rats. Akt and Erk p42/44 activation was higher in the retina of rats given 275 mg/kg GTE pre-surgery, whereas Stat3 activation was higher in those with 275 mg/kg GTE post-operation. Less activated microglia were observed in rats with pre-treatment of 275 or 550 mg/kg GTE. RNA sequencing analysis identified the downregulation of inflammation, apoptosis, and microglia activation genes in the retina of rats with pre- or post-treatment with 275 mg/kg GTE as compared to the saline-treated rats. In summary, this study revealed the prophylactic and therapeutic treatment effects of GTE on RGC survival and axonal regeneration in rats with ON injury, indicating a potential alternative treatment for traumatic optic neuropathy.

A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study).

PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

Synthesis of 4-thiosubstituted flavan derivatives and their hypoglycemic activities.

A series of 4-thiosubstituted flavan derivatives (1-44) were designed and synthesized. The target compounds were assayed for inhibitory activity against α-glucosidase in vitro, and the results indicated that all compounds displayed significant effects in the range of IC50 = 1.03-7.48 µM compared to that of acarbose, the positive control drug. Structure-activity relationship (SAR) studies indicated that the hydroxyl groups in the flavan B ring, the electron withdrawing groups, and the length of the alkyl chains are important for this biological activity. In addition, some compounds were tested for their tolerance to sucrose in mice, and compound 44 exhibited activity comparable to that of acarbose. Docking analysis indicated that compound 44 binds to the enzyme in a pocket close to the catalytic site, similar to acarbose.

[Discussion on the essential thought of Ma's warm moxibustion technique for "unblocking fu-organs"].

"Unblocking fu organs" is one of the essential principles of Ma's warm moxibustion technique, characterized as "dredging" and "harmonizing" for either deficiency or excess condition. Under the guidance of this therapeutic thought, the acupoints for moxibustion are mainly selected from the middle and lower parts of the body. Regarding the therapeutic approach, the acupoint prescription for moxibustion should be formed in line with warming and promoting circulation of fu organs; the moxibustion degree should be specially considered, in which, the mild moxibustion is recommended to induce promoting action; and the systematic moxibustion technique should be the root for dredging fu organs and regulating zang organs. Ma's mild moxibustion technique stresses on removing the obstruction of fu organs and emphasizes promoting the qi activity of sanjiao (triple energizer) and regulating the balance of five zang organs.

The phenolic acids from the plant of Salvia miltiorrhiza.

Seven new phenolic acids, 7, 8-epiblechnic acid (1), 8-epiblechnic acid 9-ehthyl-9'-methyl ester (2), 9'-ehyl-isolithospermate (3), 9''-methyl-isolithospermate (4), 9'-ethyl-9''-methyl-isolithospermate (5), 9', 9''-dimethyl-isolithospermate (6), sebesteniod E (7), were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by detailed spectroscopic means including UV, IR, HRESIMS, and NMR data spectra. The bioactive assays of compounds 1-7 against neuroprotection activities were determined. The results suggested that compound 4 exhibited a moderate glutamate-induced neuroprotective activity and the cell survival rate was 24.0% (10-5 mol/L), while compound 2 showed weak activity (survival rate: 7.58%, 10-5 mol/L), using PHPB (survival rate: 7.56%, 10-5 mol/L) as positive control.

The triterpenoids and sesquiterpenoids from the plant of Agrimonia pilosa.

A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19ß-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC50 values of 16.31 µM, 21.94 µM, and 23.40 µM, respectively.

Discussion on the essential thought of Ma's warm moxibustion technique for "unblocking fu-organs" / 中国针灸

"Unblocking fu organs" is one of the essential principles of Ma's warm moxibustion technique, characterized as "dredging" and "harmonizing" for either deficiency or excess condition. Under the guidance of this therapeutic thought, the acupoints for moxibustion are mainly selected from the middle and lower parts of the body. Regarding the therapeutic approach, the acupoint prescription for moxibustion should be formed in line with warming and promoting circulation of fu organs; the moxibustion degree should be specially considered, in which, the mild moxibustion is recommended to induce promoting action; and the systematic moxibustion technique should be the root for dredging fu organs and regulating zang organs. Ma's mild moxibustion technique stresses on removing the obstruction of fu organs and emphasizes promoting the qi activity of sanjiao (triple energizer) and regulating the balance of five zang organs.

[Research progress on chemical constituents and quality control methods of Succus Bambusae].

Through the investigation of a large number of both domestic and overseas literatures and related quality standards, chemical compositions, quality evaluation system and quality control methods of Succus Bambusae were systematic summarized in this study. There were abundant chemical constituents in Succus Bambusae, mainly including volatile ingredients, amino acids, flavonoids, trace elements and vitamins, with high medicinal and edible value. The quality control methods involved traditional morphological identification, spectroscopy, chromatography and other techniques. However, the current quality standards of Succus Bambusae are relatively low, lacking safety indicators, and cannot effectively ensure its quality, seriously affecting the safety and effectiveness of its clinical use. Therefore, it is particularly important to establish a set of highly sensitive and specific quality evaluation system for Succus Bambusae. In this paper, the current research status of the chemical compositions and quality standards of Succus Bambusae were reviewed, with the purpose of providing a basis for further improvement of its quality evaluation system.

FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons.

Background and Purpose: Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N6-methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N6-methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown. Methods: Expression of Fto mRNA and protein was assessed in mouse thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase) into unilateral thalamus. Effect of intraperitoneal administration of meclofenamic acid (a FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of Ftofl/fl mice on the Coll IV microinjection­induced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity was examined. Effect of thalamic microinjection of AAV5 expressing Fto (AAV5-Fto) on basal thalamic TLR4 expression and nociceptive thresholds was also analyzed. Additionally, level of N6-methyladenosine in Tlr4 mRNA and its binding to FTO or YTHDF2 (YTH N6-methyladenosine RNA binding protein 2) were observed. Results: FTO was detected in neuronal nuclei of thalamus. Level of FTO protein, but not mRNA, was time-dependently increased in the ipsilateral thalamus on days 1 to 14 after Coll IV microinjection. Intraperitoneal injection of meclofenamic acid or adeno-associated virus-5 expressing Cre microinjection into Ftofl/fl mouse thalamus attenuated the Coll IV microinjection­induced TLR4 upregulation and tissue damage in the ipsilateral thalamus and development and maintenance of nociceptive hypersensitivities on the contralateral side. Thalamic microinjection of AAV5-Fto increased TLR4 expression and elicited hypersensitivities to mechanical, heat and cold stimuli. Mechanistically, Coll IV microinjection produced an increase in FTO binding to Tlr4 mRNA, an FTO-dependent loss of N6-methyladenosine sites in Tlr4 mRNA and a reduction in the binding of YTHDF2 to Tlr4 mRNA in the ipsilateral thalamus. Conclusions: Our findings suggest that FTO participates in hemorrhage-induced thalamic pain by stabilizing TLR4 upregulation in thalamic neurons. FTO may be a potential target for the treatment of this disorder.

Research progress on chemical constituents and quality control methods of Succus Bambusae / 中国中药杂志

Through the investigation of a large number of both domestic and overseas literatures and related quality standards, chemical compositions, quality evaluation system and quality control methods of Succus Bambusae were systematic summarized in this study. There were abundant chemical constituents in Succus Bambusae, mainly including volatile ingredients, amino acids, flavonoids, trace elements and vitamins, with high medicinal and edible value. The quality control methods involved traditional morphological identification, spectroscopy, chromatography and other techniques. However, the current quality standards of Succus Bambusae are relatively low, lacking safety indicators, and cannot effectively ensure its quality, seriously affecting the safety and effectiveness of its clinical use. Therefore, it is particularly important to establish a set of highly sensitive and specific quality evaluation system for Succus Bambusae. In this paper, the current research status of the chemical compositions and quality standards of Succus Bambusae were reviewed, with the purpose of providing a basis for further improvement of its quality evaluation system.

Fgr contributes to hemorrhage-induced thalamic pain by activating NF-κB/ERK1/2 pathways.

Thalamic pain, a type of central poststroke pain, frequently occurs following ischemia/hemorrhage in the thalamus. Current treatment of this disorder is often ineffective, at least in part due to largely unknown mechanisms that underlie thalamic pain genesis. Here, we report that hemorrhage caused by microinjection of type IV collagenase or autologous whole blood into unilateral ventral posterior lateral nucleus and ventral posterior medial nucleus of the thalamus increased the expression of Fgr, a member of the Src family nonreceptor tyrosine kinases, at both mRNA and protein levels in thalamic microglia. Pharmacological inhibition or genetic knockdown of thalamic Fgr attenuated the hemorrhage-induced thalamic injury on the ipsilateral side and the development and maintenance of mechanical, heat, and cold pain hypersensitivities on the contralateral side. Mechanistically, the increased Fgr participated in hemorrhage-induced microglial activation and subsequent production of TNF-α likely through activation of both NF-κB and ERK1/2 pathways in thalamic microglia. Our findings suggest that Fgr is a key player in thalamic pain and a potential target for the therapeutic management of this disorder.

Three new compounds from the rhizome of Ligusticum chuanxiong and their anti-inflammation activities.

Phytochemical investigation of the rhizome of Ligusticum chuanxiong Hort led to the isolation and identification of three new compounds, chuanxiongoside A, (2E,4E)-8-(6-O-inositolyl)-8-oxo-2,7-dimethyl-octadienoic acid (2), chuanxiongoside C (3). The structures of these compounds were unambiguously established by HR-ESI-MS, UV, IR, CD, NMR spectral data and comparison to reported data. All the isolated compounds (1-3) were investigated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells. All compounds showed excellent inhibition of NO production stronger than curcumin. [Formula: see text].