Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

STUDY DESIGN: Cross-sectional and retrospective cohort study. OBJECTIVE: We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. SUMMARY OF BACKGROUND DATA: In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. PATIENTS AND METHODS: A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. RESULTS: Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). CONCLUSIONS: More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. LEVEL OF EVIDENCE: Level III.

Synergy of phosphate recovery from sludge-incinerated ash and coagulant production by desalinated brine.

Wet-chemical approach is widely applied for phosphate recovery from incinerated ash of waste activated sludge (WAS), along with metals removed/recovered. The high contents of both aluminum (Al) and iron (Fe) in WAS-incinerated ash should be suitable for producing coagulants with some waste anions like Cl- and SO42- With acid (HCl) leaching and metals' removing, approximately 88 wt% of phosphorus (P) in the ash could be recovered as hydroxylapatite (HAP: Ca5(PO4)3OH); Fe3+ in the acidic leachate could be selectively removed/recovered by extraction with an organic solvent of tributyl phosphate (TBP), and thus a FeCl3-based coagulant could be synthesized by stripping the raffinate with the original brine (containing abundant Cl- and SO42-). Furthermore, a liquid poly-aluminum chloride (PAC)-based coagulant could also be synthesized with Al3+ removed from the ash and the brine, which behaved almost the same in the coagulation performance as a commercial coagulant on both phosphate and turbidity removals. Both P-recovery from the ash and coagulant production associated with the brine would enlarge the markets of both 'blue' phosphate and 'green' coagulants.

Identification of JUN as determinant of osteoarthritis and its inhibition by the Chinese herbal formulae Zhuanggu Huoxue Tang.

Synovitis is an essential feature of Osteoarthritis (OA). Increasing evidence demonstrates that synovitis plays a critical role in OA's symptoms and structural progression. However, there is no effective drug for preventing and treating synovitis. Some Chinese herbal formulae have been found to treat clinical OA effectively, however, their mode of action is still unclear. This study investigated the Chinese herbal formulae Zhuanggu Huoxue Tang (ZHT) underlying mechanisms for treating osteoarthritis. Transcriptome data and a network pharmacology analysis were used to investigate the biochemical pathways affected by ZHT during OA treatment with in vitro verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were undertaken. The interaction network of the ZHT active constituent targets was determined using Cytoscape 3.7.1 software. Molecular docking of key pathogenic proteins and components of ZHT was performed in silico to confirm the compounds' pharmaceutical activities. The results establish that JUN is a target pathway in the pathogenesis of osteoarthritis. Miltirone, one of the active ingredients of ZHT, demonstrated a suitable binding activity with JUN. Miltirone alleviates the catabolic gene expression induced by IL-1ß and IL-6 in synovial fibroblasts (FLS), validating the use of Miltirone as a therapeutic drug for osteoarthritis.

Tangeretin suppresses osteoarthritis progression via the Nrf2/NF-κB and MAPK/NF-κB signaling pathways.

BACKGROUND: Osteoarthritis (OA) is a globally prevalent degenerative disease characterized by extracellular matrix (ECM) degradation and inflammation. Tangeretin is a natural flavonoid that has anti-inflammatory properties. Studies have not explored whether tangeretin modulates OA development. PURPOSE: The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of tangeretin. STUDY DESIGN: Effects of tangeretin on OA were detected in chondrocytes and OA mouse model. METHODS: Protective effects of tangeretin on murine articular chondrocytes treated with interleukin-1ß (IL-1ß) were evaluated using qPCR, western blot analysis, ELISA, ROS detection and immunofluorescent staining in vitro. Healing effect of tangeretin on cartilage degradation in mice was assessed through X-ray imaging, histopathological analysis, immunohistochemical staining and immunofluorescent staining in vivo. RESULTS: Tangeretin suppressed IL-1ß-mediated inflammatory mediator secretion and degradation of ECM in chondrocytes. The results showed that tangeretin abrogated destabilized medial meniscus (DMM)-induced cartilage degradation in mice. Mechanistic studies showed that tangeretin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and suppressing MAPK signaling pathway. CONCLUSION: Tangeretin abrogates OA progression by inhibiting inflammation as well as ECM degradation in chondrocytes and animal models. Effects of tangeretin are mediated through Nrf2/NF-κB and the MAPK/NF-κB pathways. Thus, tangeretin is a potential therapeutic agent for osteoarthritis treatment.

A novel hybrid scan approach enabling the ion-mobility separation and the alternate data-dependent and data-independent acquisitions (HDDIDDA): Its combination with off-line two-dimensional liquid chromatography for comprehensively characterizing the multicomponents from Compound Danshen Dripping Pill.

Data-dependent acquisition (DDA) and data-independent acquisition (DIA)-based MSn strategies are extensively applied in metabolites characterization. DDA gives accurate MSn information, but receives low coverage, while DIA covers the entire mass range, but the precursor-product ions matching often yields false positives. Currently available MS scan approaches rarely integrate DIA and DDA within a duty circle. Utilizing a Vion™ IM-QTOF (ion mobility-quadrupole time-of-flight) mass spectrometer, we report a novel hybrid scan approach, namely HDDIDDA, which involves three scan events: 1) IM-enabled full scan (MS1), 2) high-definition MSE (HDMSE) of all precursor ions (MS2); and 3) high-definition DDA (HDDDA) of top N precursors (MS2). As a proof-of-concept, the HDDIDDA approach combined with off-line two-dimensional liquid chromatography (2D-LC) was applied to characterize the multiple ingredients from a reputable Chinese patent medicine, Compound Danshen Dripping Pill (CDDP) used for treating the cardiovascular diseases. An off-line 2D-LC system by configuring an XBridge Amide column and an HSS T3 column showed a measurable orthogonality of 0.92 and enhanced the separation of co-eluting components. A fit-for-purpose HDDIDDA methodology was developed in the negative mode to characterize saponins and salvianolic acids, while tanshinones in the positive mode. Computational workflows to efficiently process the acquired HDMSE and HDDDA data were established, and the searching of an in-house CDDP library (recording 712 compounds) eventually characterized 403 components from CDDP, indicating approximate 12-fold improvement compared with the previous report. The HDDIDDA approach can measure collision cross section of each component, and merges the merits of DIA and DDA in MS2 data acquisition.

Morin attenuates osteoclast formation and function by suppressing the NF-κB, MAPK and calcium signalling pathways.

Morin is a natural compound isolated from moraceae family members and has been reported to possess a range of pharmacological activities. However, the effects of morin on bone-associated disorders and the potential mechanism remain unknown. In this study, we investigated the anti-osteoclastogenic effect of morin in vitro and the potential therapeutic effects on ovariectomy (OVX)-induced osteoporosis in vivo. In vitro, by using a bone marrow macrophage-derived osteoclast culture system, we determined that morin attenuated receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation via the inhibition of the mitogen-activated protein kinase (MAPK), NF-κB and calcium pathways. In addition, the subsequent expression of nuclear factor of activated T cells c1 (NFATc1) and c-fos was significantly suppressed by morin. In addition, NFATc1 downregulation led to the reduced expression of osteoclastogenesis-related marker genes, such as V-ATPase-d2 and Integrin ß3. In vivo, results provided that morin could effectively attenuate OVX-induced bone loss in C57BL/6 mice. In conclusion, our results demonstrated that morin suppressed RANKL-induced osteoclastogenesis via the NF-κB, MAPK and calcium pathways, in addition, its function of preventing OVX-induced bone loss in vivo, which suggested that morin may be a potential therapeutic agent for postmenopausal osteoporosis treatment.

Morin improves functional recovery after spinal cord injury in rats by enhancing axon regeneration via the Nrf2/HO-1 pathway.

Spinal cord injury (SCI) is a devastating neurological occurrence that usually leads to a loss of motor and sensory function in patients. Axon regeneration has been reported to be crucial for recovery after trauma to the nervous system. Morin, a natural bioflavonoid obtained from the Moraceae family, has previously been reported to exert neuroprotective effects. In our study, we investigated the protective effects of morin on PC12 cells and primary neurons treated with oxygen-glucose deprivation (OGD) and its function in an SCI model. In vitro experiments showed that treating neuronal cells with morin enhanced axonal regeneration after OGD treatment by regulating microtubule stabilization and protecting mitochondrial function. Mechanistically, morin protected neuronal cells exposed to OGD by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. An in vivo study illustrated that oral morin administration improved microtubule stability and promoted axon regeneration in SCI rats. Taken together, this study showed that treatment with morin improves functional recovery after SCI and that morin may serve as a potential agent for treating SCI.

α-Cyperone (CYP) down-regulates NF-κB and MAPKs signaling, attenuating inflammation and extracellular matrix degradation in chondrocytes, to ameliorate osteoarthritis in mice.

Inflammation and extracellular matrix (ECM) degradation have been implicated in the pathological process of osteoarthritis (OA). α-Cyperone is the main active component of the traditional Chinese medicine Cyperus rotundus L. In this study, we found that α-Cyperone abolished the IL-1ß-induced production of inflammatory cytokines in isolated rat chondrocytes, such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), in a dose-dependent manner (0.75, 1.5 or 3 µM). Also, the results showed that α-Cyperone downregulated the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5), and upregulated the expression of type-2 collagen. Mechanistically, molecular docking tests revealed that α-Cyperone stably and effectively binds to p65, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). α-Cyperone inhibited NF-κB activation by blocking its nuclear transfer, and decreasing the phosphorylation of mitogen-activated protein kinase (MAPKs). In addition, in vivo studies based on a mouse model of arthritis showed that α-Cyperone prevented the development of osteoarthritis. Therefore, α-Cyperone may be a potential anti-OA drug.

Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway.

Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. We used a mouse model of SCI, and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, pyroptosis, and AMPK-related signaling pathways were also examined. Our results showed that BA significantly improved functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS level and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induced mitophagy to eliminate the accumulation of ROS and inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Those results showed that BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

Comparison of the effects of general and local anesthesia in lumbar interlaminar endoscopic surgery.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) with an interlaminar approach is a technique used to treat lumbar disc hernia. It has not yet been established whether general or local anesthesia (LA) is preferable for lumbar interlaminar endoscopic surgery. METHODS: Between October, 2012 and June, 2016, 60 patients were recruited and randomly divided into 2 groups: the general anesthesia (GA) group and the LA group. The patients' basic clinical data, intraoperative patient experience, Oswestry disability index (ODI), visual analog scale (VAS) score, and the postoperative patient satisfaction rate were assessed. RESULTS: Statistically significant differences were found between the two groups in operative time and length of hospital stay. There were no significant differences in postoperative ODI or VAS scores between the two groups during follow-up at 3, 6, and 12 months. One patient in the GA group sustained a nerve root injury intraoperatively. Two patients in the LA group suffered adverse reactions, as did six patients in the GA group. However, 50% of the patients expressed fear about undergoing the surgery with LA, while all patients felt they could undergo the same surgery with GA. CONCLUSIONS: General and LA are both suitable for use in lumbar interlaminar endoscopic surgery. However, GA makes a positive intraoperative surgical experience more likely for the patient.

UFLC-MS/MS Determination and Population Pharmacokinetic Study of Tanshinol, Ginsenoside Rb1 and Rg1 in Rat Plasma After Oral Administration of Compound Danshen Dripping Pills.

BACKGROUND AND OBJECTIVES: As a traditional Chinese Materia Medica (CMM), the Compound Danshen Dripping Pill (CDDP) is widely used for the treatments of cardiovascular diseases. In view of its undefined applicable population and dosage, a population pharmacokinetic (PPK) study is required. The objective of this study was to explore the feasibility of multi-component CMM PPK in rat plasma after oral administration of CDDP based on sparse sampling. METHODS: In this research, a simple, rapid and highly sensitive UFLC-MS/MS method for the simultaneous determination of tanshinol (TSL), ginsenoside Rb1 (GRb1) and ginsenoside Rg1 (GRg1) has been successfully developed in rat plasma. Moreover, the validated method has been applied to a PPK study of CDDP based on sparse data. We established the PPK models for these three main active constituents using a nonlinear mixed-effects model, taking into account of factors such as gender, age in weeks and weight. RESULTS: The PPK models of TSL and GRb1 were best described by a one-compartment model with linear elimination and first-order absorption. The model of GRg1 was best described by a two-compartment model with first-order absorption. Bootstrap validation and a visual predictive check confirmed the predictive ability, the model stability and the precision of the parameter estimates from these models. CONCLUSION: As a preliminary exploration toward the clinical population pharmacokinetic research, this study provides a reference for the population pharmacokinetic study of traditional CMM.

The effect of Salvia miltiorrhiza in a mouse model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum.

BACKGROUND AND AIMS: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). METHODS: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-α), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-α, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. CONCLUSIONS: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS.

Simultaneous determination of three saponins in human plasma after oral administration of compound danshen dripping pills by LC-MS/MS and its application in a pharmacokinetic study.

As one of the main constituents of Compound Danshen Dripping Pills (CDDP), Panax notoginseng (PN) plays a pivotal role in the treatment of cardiovascular diseases. Numerous researches have proved that the dammarane type saponins including notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1) and ginsenoside Rb1 (GRb1) are the main bioactive components of PN in CDDP. An efficient, realiable and sensitive liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis method for simultaneously detecting NR1, GRg1 and GRb1 in human plasma was established and applied to the pharmacokinetics study of the three PN saponins after oral administration of CDDP. The human plasma samples were processed using acetonitrile and the target materials were separated on an Eclipse plus C18 column (100 × 4.6 mm, 3.5 µm) with a gradient mobile phase consisted of water (containing 0.1% formic acid) and methanol. Within the concentration ranges of 0.25-50 ng/mL, each calibration curve exhibited an excellent linear relationship (r>0.998). The precision deviations of intra-day and inter-day analysis were lower than 9.0%, and accuracy error (RE%) ranged between 1.5% and 10.5%. The average recoveries of analytes were >64.0%. The established method was successfully applied to determine the pharmacokinetics of the three saponins in human plasma. In addition to providing guidance for clinical safe medication, the experimental results also provided a valuable and reliable basis for further pharmacological studies of PN in the human body after oral administration of CDDP.

Schisandrin B attenuates epidural fibrosis in postlaminectomy rats by inhibiting proliferation and extracellular matrix production of fibroblasts.

Laminectomy has been widely considered one of the most common treatments for lumbar disorders. Epidural fibrosis (EF) is a common complication after laminectomy, causing recurrent postoperative pain. Schisandrin B (Sch.B), the active ingredient extracted from Schisandra chinensis Fructus, has been found to have potent antiproliferative and antifibrotic effects on several cells. This study aimed to investigate the effects of Sch.B on the prevention of postlaminectomy EF formation. In vitro, we studied the effects of Sch.B on transforming growth factor beta 1 (TGF-ß1)-induced proliferation and extracellular matrix (ECM) production of primary fibroblasts, as well as its underlying mechanism. We found that Sch.B not only inhibited the proliferation of fibroblasts but also reduced ECM production, including that of connective tissue growth factor, fibronectin, and type I collagen, in a dose-dependent manner. Mechanistically, we found that Sch.B suppressed TGF-ß1-stimulated activation of the Smad2/3 and mitogen-activated protein kinase pathways. Moreover, the in vivo study demonstrated that Sch.B treatment attenuated the progression of EF in a postlaminectomy rat model via reducing the cell number and ECM production of scar tissue. Taken together, these data suggested that Sch.B possesses great potential value as a preventative agent for EF.

Isolation and identification of nucleosides/nucleotides raising testosterone and NO levels of mice serum from Chinese chive (Allium tuberosum) leaves.

Our previous study found that Chinese chive could significantly (p < 0.01) raise testosterone and nitric oxide (NO) levels in mice serum. However, the specific functional components of this traditional remedy are still unknown. In order to isolate and identify the active constituents from Chinese chive for enhancing testosterone and NO levels, the Chinese chive leaves were extracted by petroleum ether, ethyl acetate, n-butanol and water respectively. Results indicated that the n-butanol extract had a significant effect on NO and testosterone blood levels. Subsequently, n-butanol extract was further isolated by D101 macroporous adsorption and eluted with 50% ethanol and then isolated by Sephadex LH-20 and preparative high-performance liquid chromatography to obtain nucleosides. The fraction eluted with 70% ethanol was further isolated by RP-18 and pre-HPLC to obtain nucleotides. Four novel compounds were identified, and their effects on testosterone and NO levels of male mice were evaluated. Results showed that nucleotides, especially the adenosine in Chinese chive leaves, increased serum testosterone and NO levels in male mice, which had not been reported before. This finding might bring into perspective the treatment strategy for those doctors who treat hormone deficiencies, and might be suitable for using in functional food.

Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells.

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.

Downregulating PI3K/Akt/NF-κB signaling with allicin for ameliorating the progression of osteoarthritis: in vitro and vivo studies.

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1ß (IL-1ß) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1ß-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.

Comparison of enhanced male mice sexual function among three medicinal materials.

To compare the effect of Epimedium brevicornum Maxim., Cynomorium songaricum Rupr. and Morindae officinalis F.C. How on enhancing sexual function effect, mice were administered gavage by the extracts from three materials, serum testosterone and nitric oxide(NO) levels in male mice were detected and the changes of sexual organs were measured. Results showed that testosterone level, NO level and sexual organs weights of Epimedium brevicornum Maxim. treatment were significantly (p < 0.01) higher than those of Cynomorium songaricum Rupr. and Morindae officinalis F. C. How treatments, which indicated that Epimedium brevicornum Maxim. was more effective to improve sexual function than the other two plants. Subsequently, Epimedium brevicornum Maxim. was selected for the second experiment, with shenbao syrup as a positive reference drug, the male sexual behaviours and female vaginal copulation plug were measured. Results showed that Epimedium brevicornum Maxim. treatment exhibited higher male capture frequency, mount frequency and vaginal plug rate, and lower capture latency and mount latency than shenbao syrup treatment, which indicated that Epimedium brevicornum Maxim. was effective to enhance male mice sexual function. Thus, this finding might bring into perspective the treatment strategy for those doctors who treat erectile dysfunction and might be suitable for use in functional food.

Structural Insights of Benzenesulfonamide Analogues as NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

NLRP3 inflammasome plays critical roles in a variety of human diseases and represents a promising drug target. In this study, we established the in vivo functional activities of JC124, a previously identified NLRP3 inflammasome inhibitor from our group, in mouse models of Alzheimer's disease and acute myocardial infarction. To understand the chemical space of this lead structure, a series of analogues were designed, synthesized, and biologically characterized. The results revealed the critical roles of the two substituents on the benzamide moiety of JC124. On the other hand, modifications on the sulfonamide moiety of JC124 are well tolerated. Two new lead compounds, 14 and 17, were identified with improved inhibitory potency (IC50 values of 0.55 ± 0.091 and 0.42 ± 0.080 µM, respectively). Further characterization confirmed their selectivity and in vivo target engagement. Collectively, the results strongly encourage further development of more potent analogues based on this chemical scaffold.