New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Qihuang Zhuyu formula alleviates coronary microthrombosis by inhibiting PI3K/Akt/αIIbß3-mediated platelet activation.

BACKGROUND: Coronary microembolism (CME) is commonly seen in the peri-procedural period of Percutaneous Coronary Intervention (PCI), where local platelet activation and endothelial cell inflammation crosstalk may lead to micro thrombus erosion and rupture, with serious consequences. Qihuang Zhuyu Formula (QHZYF) is a Chinese herbal compound with high efficacy against coronary artery disease, but its antiplatelet mechanism is unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of QHZYF on sodium laurate-induced CME using network pharmacology and in vitro and in vivo experiments. METHODS: We employed high-performance liquid chromatography mass spectrometry to identify the main components of QHZYF. Network pharmacology analysis, molecular docking and surface plasmon resonance (SPR) were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways mediating the effects of QHZYF on platelet activation. Next, we pretreated a sodium laurate-induced minimally invasive CME rat model with QHZYF. In vivo experiments were performed to examine cardiac function in rats, to locate coronary arteries on heart sections to observe internal microthrombi, to extract rat Platelet-rich plasma (PRP) for adhesion assays and CD62p and PAC-1 (ITGB3/ITGA2B) flow assays, and to measure platelet-associated protein expression in PRP. In vitro clot retraction and Co-culture of HUVECs with PRP were performed and the gene pathway was validated through flow cytometry and immunofluorescence. RESULTS: Combining UPLC-Q-TOF/MS technology and database mining, 78 compounds were finally screened as the putative and representative compounds of QHZYF, with 75 crossover genes associated with CME. QHZYF prevents CME mainly by regulating key pathways of the inflammation and platelets, including Lipid and atherosclerosis, Fluid shear stress, platelet activation, and PI3K-Akt signaling pathways. Five molecules including Calyson, Oroxin A, Protosappanin A,Kaempferol and Geniposide were screened and subjected to molecular docking and SPR validation in combination with Lipinski rules (Rule of 5, Ro5). In vivo experiments showed that QHZYF not only improved myocardial injury but also inhibited formation of coronary microthrombi. QHZYF inhibited platelet activation by downregulating expression of CD62p receptor and platelet membrane protein αIIbß3 and reduced the release of von Willebrand Factor (vWF), Ca2+ particles and inflammatory factor IL-6. Further analysis revealed that QHZYF inhibited the activation of integrin αIIbß3, via modulating the PI3K/Akt pathways. In in vitro experiments, QHZYF independently inhibited platelet clot retraction. Upon LPS induction, the activation of platelet membrane protein ITGB3 was inhibited via the PI3K/Akt pathway, revealing an important mechanism for attenuating coronary microthrombosis. We performed mechanistic validation using PI3K inhibitor LY294002 and Akt inhibitor MK-2206 to show that QHZYF inhibited platelet membrane protein activation and inflammation to improved coronary microvessel embolism by regulating PI3K/Akt/αIIbß3 pathways, mainly by inhibiting PI3K and Akt phosphorylation. CONCLUSION: QHZYF interferes with coronary microthrombosis through inhibition of platelet adhesion, activation and inflammatory crosstalk, thus has potential in clinical anti-platelet applications. Calyson, Oroxin A, Protosappanin A, Kaempferol and Geniposide may be the major active ingredient groups of QHZYF that alleviate coronary microthrombosis.

Walking exercise through smartphone application plus branched-chain amino acid supplementation benefits skeletal muscle mass and strength in liver cirrhosis: A prospective control trial.

INTRODUCTION AND OBJECTIVES: Whether a combination of exercise and branched-chain amino acid (BCAA) supplementation was more beneficial than those given alone in sarcopenia related to liver cirrhosis (LC) is unknown. Widely used smartphone applications provide continuous and easily expandable management of chronic liver disease (CLD). This study is to investigate the effects of unsupervised walking exercise using WeChat combined with BCAA supplementation on skeletal muscle mass and strength in LC. MATERIALS AND METHODS: The 127 LC patients of Child-Pugh A/B were assigned to group A (BCAA supplements, n=42), group B (walking exercise, n=43) and group C (walking exercise plus BCAA supplements, n=42). Laboratory data, average daily steps, serum BCAA, skeletal muscle mass index (SMI) and grip strength were analyzed pre- and 3 months after interventions. RESULTS: Of the 124 patients who completed interventions, albumin and daily steps were significantly increased in all groups (p=0.0001). Post-intervention BCAA were significantly elevated in group A (A vs B, p=0.001) and C (C vs B, p=0.012;). While post-intervention daily steps in group B (B vs A, p=0.0001) and C (C vs A, p=0.0001) were higher. Grip strength (C vs A, p=0.020; C vs B, p=0.036) and SMI (C vs A, p=0.035; C vs B, p=0.012) were increased in group C. Prevalence of sarcopenia was significantly decreased in group C (p=0.015). CONCLUSIONS: A combination of unsupervised walking exercise using smartphone applications and BCAA supplementation might be an effective and safe treatment for cirrhosis patients with Child-Pugh A/B to improve skeletal muscle mass and strength or to prevent progress of sarcopenia.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

Curdione ameliorates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil extracellular trap formation.

Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.

Allium vegetable intake associated with the risk of incident gastric cancer: a continuous follow-up study of a randomized intervention trial.

BACKGROUND: Allium vegetable components have antibacterial, antioxidative, and immune modulation properties, thus potentially exhibiting antitumor effects. Despite evidence from case-control studies, prospective studies linking allium vegetables with gastric cancer (GC) have been sparse. OBJECTIVE: In a prospective study, we examined whether allium vegetable intake would change the risk of GC occurrence and whether the associations would be modified by vitamin supplementation, garlic supplementation, and Helicobacter pylori (H. pylori) treatment. METHODS: The study was conducted on the basis of the Shandong Intervention Trial, a randomized, placebo-controlled, factorial-designed trial (1995-2003) in a well-recognized high-risk area for GC in China. Participants were continuously followed up to December 2017 for 22.3 y (1995-2017). A total of 3229 subjects were included, with information on the intake of allium vegetables (garlic vegetables and scallions), collected by structured questionnaires in 1994. The associations of total and individual allium vegetable intake with the risk of GC were examined, respectively. RESULTS: During the follow-up, 144 incident cases of GC were identified. Garlic vegetable intake was associated with a decreased risk of incident GC (P-trend = 0.02; OR: 0.83; 95% CI: 0.70, 0.98, per 1 kg/y increment), whereas scallion intake showed no association (P-trend = 0.80). An inverse association of the risk of GC with total allium vegetable and garlic vegetable intake was particularly stronger among those receiving the placebo for vitamin supplementation or garlic supplementation, indicating potential effect modifications by nutritional supplementation on allium vegetable intake and the risk of developing GC. Similar findings were found for analyses of the combined prevalence of dysplasia or GC. CONCLUSIONS: We found a significant reduction in the risk of developing GC with increasing dietary intake of allium vegetables, particularly garlic vegetables. The findings add to the literature on the potential inverse association of garlic vegetable intake with the risk of GC, therefore holding public health implications for dietary recommendations. This trial was registered at clinicaltrials.gov as NCT00339768.

Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via PI3K/AKT/mTOR pathway in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a primary microvascular complication of diabetes. However, a complete cure for DKD has not yet been found. Although there is evidence that Rutin can delay the onset of DKD, the underlying mechanism remains unclear. PURPOSE: To investigate the renoprotective effect of Rutin in the process of DKD and to explore its potential molecular mechanisms. METHODS: Db/db mice and high glucose (HG)-induced human renal glomerular endothelial cells (GEnCs) were used as in vivo and in vitro models, respectively. Western blot (WB), Immunohistochemistry (IHC)and Immunofluorescence (IF) staining were used to identify the expression level of proteins associated with endothelial-to-mesenchymal transition (EndMT) and autophagy. Tandem Mass Tag (TMT)-based proteomics analysis was utilized to reveal the mechanism of Rutin in DKD. Transfection with small interfering RNA (siRNA) to reveal the role of histone deacetylase 1 (HDAC1) in HG-induced GEnCs. RESULTS: Following 8 weeks of Rutin administration, db/db mice's kidney function and structure significantly improved. In HG-induced GEnCs, activation of autophagy attenuates cellular EndMT. Rutin could alleviate EndMT and restore autophagy in vivo and in vitro models. Proteomics analysis results showed that HDAC1 significantly downregulated in the 200 mg/kg/d Rutin group compared with the db/db group. Transfection with si-HDAC1 in GEnCs partially blocked HG-induced EndMT and restored autophagy. Furthermore, Rutin inhibits the phosphorylation of the PI3K / AKT/ mTOR pathway. HDAC1 overexpression was suppressed in HG-induced GEnCs after using Rapamycin, a specific mTOR inhibitor, verifying the correlation between mTOR and HDAC1. CONCLUSION: Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via the PI3K/AKT/mTOR pathway in DKD.

[Mechanism of Euodiae Fructus stir-fried with water decoction of Coptidis Rhizoma in treatment of chronic colitis based on UPLC-Q-TOF-MS, network pharmacology and experimental verification].

To elucidate the mechanism of Euodiae Fructus stir-fried with water decoction of Coptidis Rhizoma in the treatment of chronic colitis, this study employed ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, and experimental verification to predict the involved targets and signaling pathways. The chronic colitis mouse model was constructed to verify the core targets. A total of 48 compounds in the herbal medicine were identified by UPLC-Q-TOF-MS. SwissTargetPrediction was used to screen the potential active components and drug targets. GeneCards, OMIM, PharmGKB, and TDD were used to search for the disease targets. A total of 31 active ingredients, 453 targets of the herbal medicine, and 3 960 targets of chronic colitis were obtained. The common targets shared by the herbal medicine and chronic colitis were introduced into STRING to construct the protein-protein interaction(PPI) network, and CytoNCA plug-in was used to screen the key targets. A total of 90 key targets were obtained, and the key active components included isorhamnetin, quercetin, limonin, and oxyberberine. GO annotation and KEGG pathway enrichment for the key targets were carried out via DAVID. The targets were mainly involved in the positive regulation of protein phosphorylation, positive regulation of nitric oxide biosynthetic process, and negative regulation of apoptotic process. The medicine may treat chronic colitis through PI3 K-Akt, VEGF, HIF-1, and TNF signaling pathways. A mouse model of chronic colitis was established and then treated with Euodiae Fructus stir-fried with the water decoction of Coptidis Rhizoma. The experimental results demonstrated that the medicine can alleviate the pathological damage of colon, significantly reduce the levels of IL-1ß, IL-6, and TNF-α, inhibit the activation of PI3 K/Akt pathway, and down-regulate the expression of VEGFA in the treatment of chronic colitis.

Qihuang Zhuyu Formula Attenuates Atherosclerosis via Targeting PPARγ to Regulate Cholesterol Efflux and Endothelial Cell Inflammation.

At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways by using UPLC-Q-TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE-/- mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways of ApoE-/- mice and C57BL/6 wild-type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.

Antioxidative and Cytoprotective Effects of Ganoderma applanatum and Fomitopsis pinicola in PC12 Adrenal Phaeochromocytoma Cells.

Considering the impact of oxidative stress on the development of many diseases, together with the role of natural antioxidants in maintaining physiological balance in humans, medicinal mushrooms are potential sources of bioactive compounds against many diseases. In the present work, in vitro evaluation of the biological activities of the alcoholic extracts of two wild tree mushrooms, namely, Ganoderma applanatum and Fomitopsis pinicola, has been performed. Extraction of G. applanatum (GAE) and F. pinicola (FPE) was conducted with 60% ethanol and 100% ethanol sequentially. UPLC-MS/MS identification was conducted on the two mushrooms extracts. A total of 15 substances were identified in GAE, including 3 spiro meroterpenoids and 12 triterpenoids; a total of 14 chemical constituents were iden¬tified in FPE, including 8 triterpenoids, 4 triterpene glycosides, 1 lanosterol, and 1 lanostanoid. The resulting extracts were examined for their in vitro antioxidative and cytoprotective effects against AAPH-induced oxidative damage. Our results demonstrated that both extracts have potent antioxidative activities, when GAE was 0.2 mg/mL, the clearance rates of DPPH and ABTS have reached 93.34% and 99.93%, respectively. When FPE was 1.4 mg/mL and 0.6 mg/mL, the scavenging rates of DPPH and ABTS have reached 91.76% and 100%, respectively. Both the alcoholic extracts of G. applanatum and F. pinicola were able to protect the AAPH-induced damage and could effectively inhibit cell aging via ß-galactosidase (SA ß-gal) staining activity test and scanning electron microscopy analysis.

Risk tradeoffs between nitrogen dioxide and ozone pollution during the COVID-19 lockdowns in the Greater Bay area of China.

Photochemical regime for ozone (O3) formation is complicated in the sense that reducing emission of nitrogen oxides (NOx) may increase O3 concentration. The lockdown due to COVID-19 pandemic affords a unique opportunity to use real observations to explore the O3 formation regime and the effectiveness of NOx emission control strategies. In this study, observations from ground networks during the lockdowns were used to assess spatial disparity of the Ratio of Ozone Formation (ROF) for nitrogen dioxide (NO2) reduction in the Greater Bay Area (GBA) of China. The health risk model from Air Quality Health Index (AQHI) system in Hong Kong was adopted to evaluate the risk tradeoffs between NO2 and O3. Results show that the levels of O3 increase and NO2 reduction were comparable due to high ROF values in urban areas of central GBA. The ozone reactivity to NO2 reduction gradually declined outwards from central GBA. Despite the O3 increases, the NOx emission controls reduced the Integrated Health Risk (IHR) of NO2 and O3 in most regions of the GBA. When risk coefficients from the AQHI in Canada or the global review were adopted in the risk analyses, the results are extremely encouraging because the controls of NOx emission reduced the IHR of NO2 and O3 almost everywhere in the GBA. Our results underscore the importance of using a risk-based method to assess the effectiveness of emission control measures and the overall health benefit from NOx emission controls in the GBA.

Yishen Huashi Granules Ameliorated the Development of Diabetic Nephropathy by Reducing the Damage of Glomerular Filtration Barrier.

Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the primary cause of end-stage renal disease. At present, renin-angiotensin-aldosterone system (RAAS) blockers have been applied as first-class drugs to restrain development of DN; however, its long-term effect is limited. Recent evidence has shown definite effects of Chinese medicine on DN. Yishen Huashi (YSHS) granule is a traditional Chinese Medicine prescription that has been used in the clinic to treat DN, but its mechanism is not understood. Methods: In the present study, both in vitro and in vivo studies were carried out. The DN model was induced by STZ in Wistar rats, and GEnC and HPC cell lines were applied in the in vitro study. Quality of YSHS was evaluated by LC-MS/MS. A metabolomic study of urine was carried out by LC-MS; influence of YSHS on composition of DN was analyzed by network pharmacology. Mechanism of the YSHS on DN was analyzed by Q-PCR, Western Blot, and multi-immunological methods. Results: We found YSHS administration significantly reduced levels of HbA1c and mALB. Histopathological analysis found that YSHS preserved integrity of glomerular filtration barrier by preserving viability of glomerular endothelial cells and podocytes, inhibiting glomerular fibrosis, reducing oxidative stress damage, and enhancing cross-talk among glomerular endothelial cells and podocytes. Network pharmacology, differential metabolite analysis, as well as intracellular pathway experimental study demonstrated that the PI3K/AKT/mTOR signaling pathway played a pivotal role in it. Conclusion: Our present findings supplied new understanding toward the mechanism of YSHS on inhibiting DN.

A potential link between plasma short-chain fatty acids, TNF-α level and disease progression in non-alcoholic fatty liver disease: A retrospective study.

The onset and progression of non-alcoholic fatty liver disease (NAFLD) remains unclear, but short-chain fatty acids (SCFAs) in circulation may participate in its pathogenesis by acting as inflammation inhibitors. The aim of this retrospective study was to investigate plasma concentrations of general SCFAs in healthy individuals and in patients with distinct stages of NAFLD. Three main SCFAs (including acetate, propionate and butyrate) were analyzed by gas chromatography. The plasma TNF-α concentration was measured by ELISA. One-way ANOVA, Spearman's correlation and Pearson's correlation analysis were performed to estimate the associations between SCFAs, TNF-α and disease progression. Multiple linear stepwise regression was computed to explore the predictor variables of TNF-α in circulation. A total of 71 patients with NAFLD [including 27 patients with NAFL, 20 patients with non-alcoholic steatohepatitis (NASH) and 24 patients with NAFLD-related cirrhosis (NAFLD-cirrhosis)] and 9 healthy control (HC) subjects were enrolled for analysis. Although not statistically significant, plasma SCFAs were elevated in patients with NAFL compared with HC subjects, whereas the vast majority of SCFAs were statistically reduced in patients with NASH or NAFLD-cirrhosis compared with patients with NAFL. Plasma SCFAs had no significant differences in NASH or NAFLD-cirrhosis patients compared with HC subjects. In addition, significant negative correlations were observed between TNF-α and SCFAs. The progression of NAFLD (ß=0.849; P<0.001) and the decline of the total three SCFA concentrations (ß=-0.189; P<0.001) were recognized as independent risk variables related to the elevated peripheral TNF-α in the multiple linear stepwise regression model. Plasma SCFA concentrations may alter with the development of NAFLD and may have a potential link to TNF-α and the progression of NAFLD, which may serve a protective role toward disease advancement. Further mechanistic studies, such as analysis of gastrointestinal microecology, signaling pathways and functions involved in TNF-α, need to be performed. Also, therapeutic supplementation of SCFAs for NASH and NAFLD-cirrhosis needs further research and verification.

Genus Spatholobus: a comprehensive review on ethnopharmacology, phytochemistry, pharmacology, and toxicology.

Edible medicinal plants are important sources for the development of health beneficial products and drugs. Several species of the genus Spatholobus are considered as medicinal and food homologous plants in various Asian countries for the treatment of menstrual pain, anemia, paralysis, arthralgia, etc. Regarding this genus, mounting investigations on different aspects have been conducted; however, a comprehensive review about these findings is yet to be compiled. Herein, we reviewed the up-to-date information on the botanical description, distribution, ethnopharmacology, phytochemistry, pharmacology, and toxicology of the Spatholobus species for the first time to support their development potential. Thus far, 175 phytochemicals have been isolated, and flavonoids are the predominant constituents. Furthermore, 141 compounds show the ideal characteristic behavior of a drug-like molecule. Besides, the compounds and crude extracts of this genus have been demonstrated to exert a wide range of in vitro and in vivo bioactivities, such as antitumor activity, antioxidant activity, antiinflammatory activity, antiischemic activity, antimicrobial activity, and neuroprotective activity. Toxicity studies have revealed that Spatholobus species seem to have no apparent toxic effects. Even so, the need for in-depth studies to reveal the scientific connotation of the widely documented traditional actions, the structure-activity relationship of the bioactive compounds, and the systematic toxic reactions are warranted, and also to provide essential evidence for the beneficial use of Spatholobus plants and developing novel health care products and therapeutic drug from this genus.

Combination of Sanguisorbigenin and Conventional Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus: Inhibition of Biofilm Formation and Alteration of Cell Membrane Permeability.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is challenging to eradicate because of antibiotic resistance and biofilm formation. Novel antimicrobial agents and alternative therapies are urgently needed. This study aimed to evaluate the synergy of sanguisorbigenin (SGB) isolated from Sanguisorba officinalis L. with six conventional antibiotics to achieve broad-spectrum antibacterial action and prevent the development of resistance. A checkerboard dilution test and time-to-kill curve assay were used to determine the synergistic effect of SGB combined with antibiotics against MRSA. SGB showed significant synergy with antibiotics and reduced the minimum inhibitory concentration of antibiotics by 2-16-fold. Biofilm inhibition assay, quantitative RT-PCR, crystal violet absorption, and transmission electron microscopy were performed to evaluate the synergy mechanism. The results indicated that SGB could inhibit biofilm formation and alter cell membrane permeability in MRSA. In addition, SGB was found to exhibit quite low cytotoxicity and hemolysis. The discovery of the superiority of SGB suggests that SGB may be an antibiotic adjuvant for use in combination therapy and as a plant-derived antibacterial agent targeting biofilms.

Astragaloside IV Improves the Barrier Damage in Diabetic Glomerular Endothelial Cells Stimulated by High Glucose and High Insulin.

Objective: To investigate the protective effect and mechanism of astragaloside IV (AS-IV) on damage in human glomerular endothelial cells (GEnCs) stimulated by high glucose and high insulin. Methods: The transwell method was used to detect the integrity of the cell barrier after AS-IV intervention in a high glucose and high insulin environment for 24 h; immunofluorescence and Western blot methods were used to detect the tight junction protein ZO-1 and claudin-5 expression; intracellular and extracellular 1ß (IL-1ß) and tumor necrosis factor α (TNFα) were determined by ELISA; expression and activation of AKT, p-AKT, GSK3α/ß, and p-GSK3α/ß were evaluated by Western blot. Results: The results showed that AS-IV had a significant protective effect on the cell barrier of GEnCs. High glucose or insulin inhibited cell viability in a concentration-dependent manner. High glucose or insulin significantly inhibited glucose uptake and promoted release of reactive oxygen species in GEnCs. Administration with AS-IV dramatically preserved viability of the cells; moreover, the expression of intracellular tight junction proteins was upregulated, inflammatory cytokines including IL-1ß and TNFα were decreased, and the AKT-GSK3 pathway participated in modulation of AS-IV in GEnCs cells. Conclusion: We found in the present study that AS-IV can preserve filtration barrier integrity in glomerular endothelial cells under diabetic settings, its effects on increasing the cell energy metabolism and cell viability, inhibiting inflammation and oxidative stress damage, and enhancing tight junction between cells play a role in it; and the intracellular signaling pathway AKT-GSK modulated the above function. Our present finding supplied a new understanding towards development of DN and provided an alternative method on ameliorating DN.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

A systematic review and meta-analysis of acupuncture combined with Tuina in the treatment of insomnia.

BACKGROUND: Insomnia is a sleep disorder with insufficient sleep time or/and poor sleep quality. Relevant epidemiological studies have shown that insomnia symptoms occur in about 35% to 50% of the adult population, and it is one of the most common diseases in the elderly. Patients who often suffer from insomnia are prone to symptoms such as fatigue, weakened cognitive function, depression, and even mental illness, which bring serious physical and mental damage to individuals and a heavy economic burden to social medical care and families. Traditional Chinese medicine and modern medicine have their own advantages in the treatment of insomnia, and there is currently a lack of reports on the comparison of acupuncture combined with massage and conventional medicine. OBJECTIVE: To evaluate the clinical efficacy of acupuncture combined with Tuina in the treatment of insomnia. METHODS: Search for clinical randomized controlled trials (RCTs) of acupuncture combined with Tuina in the treatment of insomnia from PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, and China Science and Technology Journal Database. The RevMan5.4 software was used for Meta- analysis after literature screening, data extraction and quality evaluation. RESULTS: A total of 29 studies were included with a total of 2688 cases. Compared with drugs or acupuncture alone, acupuncture combined with Tuina has advantages in the total clinical effectiveness, as well as the Pittsburgh Sleep Quality Index (PSQI) and Statistical Self-Rating Anxiety Scale score (SAS) (OR = 3.59, 95% confidence interval [CI] [2.77, 4.66], Z = 9.62 [P < .00001]) (MD = -2.44, 95% CI [-2.93, -1.95], Z = 9.72 [P < .00001]) (MD = -8.42, 95% CI [-10.23, -6.61], Z = 9.09 [P < .00001]). There was no statistically significant difference in Statistical Self-rating Depression Scale score (SDS) (MD = -5.26, 95% CI [-11.29, 0.78], Z = 1.71 [P > .05]). CONCLUSION: Acupuncture combined with Tuina has obvious clinical advantages in the treatment of insomnia. This result is expected to provide a reference for the clinical treatment of insomnia, but the long-term effect of clinical efficacy still needs further study.

Eleutheroside K Isolated from Acanthopanax henryi (Oliv.) Harms Inhibits the Expression of Virulence-Related Exoproteins in Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is a representative pathogen that produces numerous virulence factors involving manifold cytotoxins and exotoxins. The present study was designed to investigate the influence of Eleutheroside K (ETSK), a single compound isolated from the leaves of Acanthopanax (A.) henryi (Oliv.) Harms, on the exotoxins secreted by MRSA. The transcription and translation of the exotoxins (α-hemolysin and staphylococcal enterotoxins) related to virulence in S. aureus were determined via quantitative RT-PCR and western blot analysis. The effect of ETSK on the production of tumor necrosis factor (TNF)-α was evaluated using enzyme-linked immunosorbent assay. As a result, ETSK at sub-MIC concentrations could reduce the protein expression of α-hemolysin and enterotoxin, and the expression of genes that regulate virulence factors was also inhibited. In addition, the TNF-inducing activity of S. aureus was attenuated by ETSK in a dose-dependent manner. These results revealed that ETSK not only reduced the protein and gene expression levels of related exotoxins but also suppressed the ability of S. aureus to induce macrophages to release cytokines. This study indicated that the inhibition of MRSA infection by ETSK may be achieved by reducing the virulence of S. aureus and highlighted the potential of ETSK as an innovative strategy for the prevention and treatment of MRSA infections.

The potential role of melatonin in retarding intervertebral disc ageing and degeneration: A systematic review.

Intervertebral disc degeneration (IDD) is a common degenerative disease of the musculoskeletal system that develops with age. It is regarded as the main cause of chronic low back pain in the elderly. IDD has various causes, including ageing, mechanical overloading, and nutritional deficiency. Melatonin is a pleiotropic indole hormone secreted by the pineal gland and plays an important role in resisting various degenerative diseases. The serum levels of melatonin decline with age and are reported to be negatively correlated with the symptomatic and histopathological scores of IDD. In vivo studies have shown that exogenous administration of melatonin could maintain the structural integrity of the intervertebral disc and inhibit the development of IDD. Mechanistically, by interacting with its membrane or intracellular receptors, melatonin can promote autophagic flux, scavenge free radicals, inhibit the release of pro-inflammatory factors, and block apoptotic pathways, thereby enhancing anti-stress abilities and matrix anabolism in different types of disc cells. Therefore, melatonin supplementation may be a promising therapeutic strategy for IDD. This review aimed to summarize the latest findings regarding the therapeutic potential of melatonin in IDD.