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Abstract: A highly sensitive and specific method of rapid resolution liquid chromatography tandem mass spectrometry (RRLC–MS/MS) in positive ionization mode has been developed and validated for pharmacokinetic study of puerarin in rat plasma. Chromatography was carried out on a Zorbax XDB C18 reversed-phase column using a mobile phase comprising a mixture of methanol and 0.05% acetic acid in water (35:65, v/v) with a flow rate of 0.3mL/min from 0min to 5.4min and then 0.6mL/min from 5.41min to 12min. The mass spectrometer operated in ESI positive ionization mode. Multiple reaction monitoring (MRM) was used to measure puerarin and tectoridin (internal standard). The method was sensitive with a detection limit of 0.33ng/mL. A good linear response was observed over a range of 10–2000ng/mL in rat plasma. The inter- and intra-day precision ranged from 2.97% to 7.52% and accuracy from 93.70% to 101.60%. This validated method was applied successfully to a pharmacokinetic study in rat plasma after intravenous administration of puerarin. The main pharmacokinetic parameters were as follows: AUC0→t 45.37±13.19 (mgh/L), AUC0→∞ 47.03±14.78 (mgh/L), MRT 1.03±0.46 (h), T 1/2 1.31±0.31 (h), V ss 0.09±0.02 (L), V z 0.17±0.04 (L), Cl 0.10±0.04 (L/h). [Copyright &y& Elsevier]

Abstract: Puerarin has various pharmacological effects; however, poor water-solubility and low oral bioavailability limit its clinical utility. A delivery system of solid lipid nanoparticles could enhance its oral absorption. The objective of this study was to investigate the pharmacokinetics, tissue distribution and relative bioavailability of puerarin in rats after a single dose intragastric administration of puerarin solid lipid nanoparticles (Pue-SLNs). The puerarin concentrations in plasma and tissues were determined by rapid resolution liquid chromatography electrospray ionization–tandem mass spectrometry. The C max value of puerarin after the administration of Pue-SLNs was significantly higher than that obtained with puerarin suspension (0.33±0.05μg/mL vs. 0.16±0.06μg/mL, P <0.01). The T max value after the administration of the Pue-SLNs was significantly shorter than that after puerarin suspension administration (40±0min vs. 110±15.49min, P <0.01). The AUC0→t values of puerarin were 0.80±0.23mgh/L, and 2.48±0.30mgh/L after administration of the puerarin suspension and Pue-SLNs, respectively. Following administration of the Pue-SLNs, tissue concentrations of puerarin also increased, especially in the target organs such as the heart and brain. These data suggest that SLNs are a promising delivery system to enhance the oral bioavailability of puerarin. [Copyright &y& Elsevier]

Endothelial dysfunction is related to reduced arterial elasticity in patients with essential hypertension. Circulating endothelial progenitor cells (EPCs), an important endogenous repair approach for endothelial injury, is altered in hypertensive patients. However, the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity has not been reported. The purpose of this study is to investigate the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity. We measured the artery elasticity profiles including brachial-ankle PWV (baPWV) and C1 large and C2 small artery elasticity indices in patients with essential hypertension (n = 20) and age-matched normotensive subjects (n = 21). The number and activity of circulating EPCs isolated from peripheral blood were determined. Compared to normotensive subjects, the patients with hypertension exhibited decreased C1 large and C2 small artery elasticity indices, as well as increased baPWV. The number of circulating EPCs did not differ between the two groups. The migratory and proliferative activities of circulating EPCs in hypertensive patients were lower than those in normotensive subjects. Both proliferatory and migratory activities of circulating EPCs closely correlated with arterial elasticity profiles, including baPWV and C1 large and C2 small artery elasticity indices. Multivariate analysis identified both proliferative and migratory activities of circulating EPCs as independent predictors of the artery elasticity profiles. The present study demonstrates for the first time that impaired activity of circulating EPCs is associated with reduced arterial elasticity in patients with hypertension. The fall in endogenous repair capacity of vascular endothelium may be involved in the pathogenesis of hypertension-related vascular injury. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, a natural compound isolated from turmeric, may inhibit cell proliferation in various tumor cells through a mechanism that is not fully understood. The enhancer of zeste homolog 2 (EZH2) gene is overexpressed in human breast cancers with poor prognosis. In this study, we observed a dose- and time-dependent down-regulation of expression of EZH2 by curcumin that correlates with decreased proliferation in the MDA-MB-435 breast cancer cell line. The curcumin treatment resulted in an accumulation of cells in the G1 phase of the cell cycle. Further investigation revealed that curcumin-induced down-regulation of EZH2 through stimulation of three major members of the mitogen-activated protein kinase (MAPK) pathway: c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. These data suggest that an underlying mechanism of the MAPK pathway mediates the down-regulation of EZH2, thus contributing to the anti-proliferative effects of curcumin against breast cancer. [Copyright &y& Elsevier]

Abstract: The objective of this work was to investigate the color, transparency, water sensitivity and mechanical properties stability in air under photo-oxidative degradation influencing consumer acceptance and biodegradation behaviors in soil of soy protein isolate (SPI)/poly (vinyl alcohol) (PVA) blend packaging films during 30 days. The results showed that PVA could dilute the yellow color and make the SPI-based films less darkness in application and the transparency of SPI/PVA films at various stages of degradation was improved. The addition of PVA decreased the ability of SPI protein molecules to absorb water and enhanced the mechanical properties of blend films comparing to pure SPI film in 30 days. Aerobic biodegradation of films in soil proved that the PVA compound interacting with protein imposed negative effects on biodegradation of blend films prolonging their decomposing time. The SPI/PVA blend films decomposed into small fragments of less complex molecules along with surface completely digested after 30 days. [Copyright &y& Elsevier]

Abstract: Three novel zinc coordination polymers (NH4) n [Zn(Hida)Cl2] n (1), [Zn(ida)(H2O)2] n (2), [Zn(Hida)2] n ·4nH2O (3) (H2ida=iminodiacetic acid) and a monomeric complex [Zn(ida)(phen)(H2O)]·2H2O (4) (phen=1,10-phenanthroline) have been synthesized and characterized by X-ray diffraction methods. 1 and 2 form one-dimensional (1-D) chain structures, whereas 3 exhibits a three-dimensional (3-D) diamondoid framework with an open channel. The mononuclear complex 4 is extended into a 3-D supramolecular architecture through hydrogen bonds and π–π stacking. Interestingly, cyclic nonplanar tetrameric water clusters are observed that encapsulated in the 3-D lattice of 4. Based on 1H and 13C NMR observations, there is obvious coordination of complex 2 in solution, while 1 and 3 decompose into free iminodiacetate ligand. Monomer [Zn(ida)(H2O)3] (5) is considered as a possible discrete species from 2. These coordination polymers can serve as good molecular precursors for zinc oxide. [Copyright &y& Elsevier]

Abstract: A special method “conduit synthesis technology” has been utilized to produce spherical nickel hydroxide powders with different chemical compositions. Three kinds of powers A, B, C were prepared by chemically coprecipitating Ni, Co, Zn, Ca, Mg and Cu. It was found that powder B produced better performance than the others. The discharge capacities of powder B could achieve 280mAhg−1 for both 1C and 2C rates at 65°C, respectively. The cyclic voltammetry analysis showed that the difference between the oxidation potential and the oxygen evolution potential of powder B is 122mV. It indicated that Co could improve conductivity of electrons, restrict the oxygen evolution reaction and thus promote the high rate charge/discharge and high-temperature performance. Ca and Mg might effectively enhance the oxygen evolution potential in the charge process. Furthermore, the proper addition of Zn, Ca and Cu could lower the ionization energy and elevated the transition energy, and thus the transfer of electrons in electrode materials was accelerated and the electrochemical performance of nickel hydroxide electrode was improved. It was a promising way to improve the electrochemical performance of spherical nickel hydroxide for Ni–MH batteries. [Copyright &y& Elsevier]

Gut dysbiosis and dysregulation of gut–brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects. [Display omitted] • Curcumin ameliorated hypertension and cardiac hypertrophy. • Curcumin altered composition of intestinal microbiota and reshaped gut microbiome. • Curcumin attenuated neuroinflammation and oxidative stress in the PVN. • Microbiota-gut-brain axis are involved in the antihypertensive effect of curcumin. [ABSTRACT FROM AUTHOR]

In situ microprobe Raman and XRD techniques were used to follow the oxidation state of Rh/Al2O3 and Ru/Al2O3 catalysts during the catalytic ignition process of the partial oxidation of methane (POM) to synthesis gas. It was found that the catalyst was in the fully oxidized state before ignition of the POM reaction, and abruptly changed its oxidation state at the temperature at which the POM reaction started. After the POM reaction was ignited, the amount of Rh2O3 or RuO2 in the catalyst at the entrance of the catalyst bed was below the detection level of Raman spectroscopy. Due to the greater Mrength of Rud with Rhce:inf loc="post">2O3 demonstrated a greater tendency to oxidize than Rh/Al2O3 under the POM conditions. This factor affects the oxygen coverage on the two catalysts under reaction conditions and consequently affects the pathways of synthesis gas formation. [Copyright &y& Elsevier]

Poor oral bioavailability is a major limitation for the successful use of flavonoids as cancer chemopreventive agents. Recently we demonstrated that fully methylated flavones have greatly increased metabolic stability and intestinal transport. However, their effects on cancer cell proliferation are not well understood. In the present study we compared the effects of fully methylated versus unmethylated flavones on oral cancer cell proliferation, using BrdU incorporation into newly synthesized DNA as the assay. In the human oral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were ten times more potent inhibitors of cell proliferation (IC50 5-8 µM) than the corresponding unmethylated analogs chrysin and apigenin. Several other methylated flavones also inhibited cell proliferation but were less potent. Cell cycle analysis showed that both 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone arrested the SCC-9 cells in G1 phase with a concomitant decrease in S phase, dramatically different from the unmethylated analogs which promoted G2/M arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines but had very poor effectiveness in two immortalized normal cell lines. Thus, some bioavailable, fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Exercise and food supplement of vitamin C (VC) are beneficial to human health, especially for those who suffer from hypertension. Here we tend to explore if gut microflora is involved in the anti-hypertensive effects of exercise and VC-supplement therapies. With the spontaneously hypertensive rat (SHR) model, the small intestine pathology and the fecal microbiota was analyzed along with the pro- and anti-inflammatory cytokines (PICs and AICs) and reactive oxygen species (ROS) in the hypothalamus paraventricular nucleus (PVN) and intestine. We found that both exercise and VC intake, individually or combined, were able to alleviate the blood pressure in the SHRs comparing to the normotensive control Wistar-kyoto (WKY) rats. The expression level of PICs in the PVN and intestine of the SHRs was down-regulated while the AICs were up-regulated after treatments, together with down-regulation of ROS in the PVN. At meantime, the gut pathology was dramatically improved in the SHRs with exercise training or VC intake. Analysis of the gut microflora revealed significant changes in their composition. Several important micro-organisms that were deficient in the SHRs were found up-regulated by the treatments, including Turicibacter and Romboutsia which are involved in the short-chain fatty acid production. Exercise training and VC intake individually can modify the gut microflora composition and improve the inflammatory state in both PVN and intestine, which contribute to their anti-hypertensive function. Combination of the two treatments enhanced their effects and worth to be considered as a non-medical aid for the hypertensive patients. [ABSTRACT FROM AUTHOR]

Describes the significance in human, scientific and technical terms of the first experiment in telerobotic surgery in July 7, 1993. Remote control of a robot in Milan, Italy by a surgeon in Pasadena, California; Goal of performing a surgical operation on a model containing a pig's organs; Double satellite link transmission.

The preservation of anammox granules is of great significance for the rapid start-up of the anammox process and improvement of performance stability. Therefore, it is necessary to explore an economical and stable preservation strategy. Exogenous extracellular polymeric substances (EPS) were used as protective agents for the preservation of anammox granules in this study. In brief, EPS from anammox sludge (A-EPS) and denitrifying sludge (D-EPS) were added to preserve anammox sludge at 4 °C and room temperature (15–20 °C). The results showed that A-EPS addition at 4 °C was the optimal condition for the preservation of anammox granules. After 90 days of preservation, the specific anammox activity (SAA) of the anammox granules remained at 92.7 ± 2.2 mg N g−1 VSS day−1 (remaining ratio of 33.4%), while that of the sludge with D-EPS addition at the same temperature was only 77.1 ± 3.2 mg N g−1 VSS day−1 (remaining ratio of 27.8%). The nitrogen removal efficiency of the experimental group with D-EPS at room temperature was 85.9%, and that of the A-EPS group reached 90.6% under the same temperature conditions. The abundance of the functional genes hzs A, hdh and nir S of the sludge (4 °C; A-EPS addition) after recovery were 138.5%, 317.1%, and 375.9%, respectively, of those of sludge from the D-EPS-added group at the same temperature. RDA revealed the contribution of proteins to the preservation process. Overall, this study provides an economical and robust strategy for the preservation of anammox granules. Unlabelled Image • Exogenous EPS was used as protective agents for the anammox sludge preservation. • Addition of exogenous EPS significantly increased anammox activity in short term. • Adding A-EPS at 4 °C led to the optimal recovery performance. • The protein in EPS is a potential factor in optimizing preservation performance. [ABSTRACT FROM AUTHOR]

A novel amphiphilic camptothecin prodrug that spontaneously arranges into nanomicelles which preferentially release the cytotoxic drug under tumor-relevant reductive conditions is designed. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) ranks the most commonly diagnosed and highest mortality-leading cancer worldwide despite a variety of treatment strategies are available. The highly heterogeneous and aggressive property of NSCLC as well as its poor prognosis indicates the need for novel therapeutic targets identification. The objective of this study is to identify potential targets from the adjuvant herbal formula BL02 using a combined approach of high throughput transcriptomics and network pharmacology. The quality and stability of BL02 were assessed by UHPLC analysis. The inhibitory effect of BL02 on NSCLC was measured by in vivo orthotopic intrathoracic mouse model and in vitro cellular models. EGFR -mutant HCC827 and wild type A549 cell lines were employed. Transcriptomics analysis was introduced to profile the gene expression of NSCLC cells treated with BL02; Network pharmacology and molecular docking analyses predicted the interaction of compounds and NSCLC targets. Immuno-blotting and pull-down assays verified the putative targets. The UHPLC analysis revealed that BL02 was relatively stable between batches of production and for 24 months of storage. Orally administration of BL02 was safe and effective to inhibit pulmonary NSCLC growth in mice implanted with A549 and HCC827-generated tumors. BL02 exhibited relatively low cytotoxicity to NSCLC cells in vitro , but potently suppressed NSCLC cell motility. The transcriptomic analysis illustrated that EGFR and cellular adhesion-related signaling is involved in BL02 action. Further bioinformatics analysis validated BL02 activity is mediated by cdc42-regulated signaling. BL02 depolymerized the actin cytoskeleton through suppressing cdc42 and deactivating its upstream molecule Rap1. These effects may be primarily mediated by the direct binding of 5-methylcoumarin-4-cellobioside and mangiferin from BL02 to Rap1 protein. Our study proposes an integration model of experimental, transcriptomic and bioinformatics analyses in the identification of novel therapeutic target of NSCLC from an adjuvant herbal formula BL02. Our findings revealed that inhibition of Rap1/cdc42 signaling by active compounds 5-methylcoumarin-4-cellobioside and mangiferin from BL02 might be potentially effective therapy for NSCLC. [ABSTRACT FROM AUTHOR]

The hypothalamic paraventricular nucleus (PVN) plays crucial roles in central cardiovascular regulation. Increasing evidence in humans and rodents shows that vitamin D intake is important for achieving optimal cardiovascular function. The purpose of this study was to investigate whether calcitriol, an active form of vitamin D, improves autonomic and cardiovascular function in hypertensive rats and whether PVN oxidative stress and inflammation are involved in these beneficial effects. Male spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were treated with either calcitriol (40 ng/day) or vehicle (0.11 μL/h) through chronic PVN infusion for 4 weeks. Blood pressure and heart rate were recorded continuously by radiotelemetry. PVN tissue, heart and plasma were collected for molecular and histological analysis. Compared to WKY rats, SHR exhibited increased systolic blood pressure, sympathetic drive, and cardiac hypertrophy and remodeling. These were associated with higher mRNA and protein expression levels of high mobility box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), proinflammatory cytokines, NADPH oxidase subunit in the PVN. In addition, increased norepinephrine in plasma, elevated reactive oxygen species levels and activation of microglia in the PVN were also observed in SHR. Chronic calcitriol treatment ameliorated these changes but not in WKY rats. Our results demonstrate that chronic infusion of calcitriol in the PVN ameliorates hypertensive responses, sympathoexcitation and retains cardiovascular function in SHR. Reduced inflammation and oxidative stress within the PVN are involved in these calcitriol-induced effects. • PVN infusion of calcitriol ameliorates autonomic dysfunction and hypertension. • Chronic calcitriol treatmen attenuates cardiac hypertrophy and remodeling. • Chronic calcitriol treatment reduces PVN neuroinflammation and oxidative stress. • HMGB1-RAGE/TLR4-NF-κB axis in PVN is associated with the effects of calcitriol. [ABSTRACT FROM AUTHOR]

Persulfate based advanced oxidation process is a promising technology for refractory contaminants removal. Cobalt is considered as the most efficient metal in catalyzing peroxymonosulfate decomposition. Although different cobalt based nanomaterials have been developed, easy aggregation and metal ion leaching during catalytic reaction would result in its deficiency. To address the above issue, in this work, carbon supported Co/CoO core-shell nanocomposite was in-situ fabricated by using polyphenol-metal coordinate as precursor. Results indicated that cobalt nanoparticle with size of 10 nm was successfully prepared and well dispersed within the carbon matrix. By using as-prepared material as catalyst, 50 mg/L orange II was completely removed under the condition of 0.2 g/L peroxymonosulfate, 0.05 g/L catalyst, pH = 4.0–10.0. Both sulfate and hydroxyl radicals were formed during peroxymonosulfate decomposition, while sulfate radical dominated the pollutant removal. Mechanism study revealed that the cobalt was the key site for catalyzing peroxymonosulfate decomposition. This work might provide valuable information in designing and fabricating metal anchored carbon composite catalyst for efficiently and cost-effectively activate peroxymonosulfate. Image 1 • Co/CoO core-shell nanostructure was well dispersed within the carbon matrix. • Co/CoO@C nanocomposite remains stable within pH ranges of 4.0-10.0, rather than the current 4.0-7.0. • Sulfate radical was the dominant reactive species for orange II removal. • Peroxymonosulfate catalytic decomposition mechanism was explored and clarified. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common disorder of the urinary system in aging men. 2-(1H-indol-3-yl)-N-[3-(4-(2-methoxyphenyl) piperazinyl) propyl] acetamide (HJZ-3), which is derived from naftopidil, exhibited 97.7- and 64.6-fold greater inhibitory effects for a 1D adrenoceptor than for a 1B - and a 1A -adrenoceptors in vitro, respectively. To investigate the therapeutic potential for treating BPH, we evaluated the pharmacological activity of HJZ-3. Specifically, we evaluated through estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo. HJZ-3 effectively prevented the progression of rat prostatic hyperplasia by suppressing the increase in prostate index and reducing the quantitative analysis of the relative acinus volume, relative stroma, epithelial volume and epithelial thickness and expression of proliferating cell nuclear antigen and α -smooth muscle actin. HJZ-3 decreased α 1A - and α 1D -adrenoceptor protein expressions in prostate tissue. HJZ-3 is a good alternative for α 1A - and α 1D -adrenoceptor blocker. It may relax smooth muscle tone and relieve symptoms of BPH. [ABSTRACT FROM AUTHOR]

A recently designed "industry-scale microfluidizer" (ISM) was applied to treat potato starch, then the structural and physicochemical properties of potato starch treated at different ISM pressure (30, 60, 90, and 120 MPa) were investigated. As ISM pressure increased, starch granule size was firstly increased, and subsequently declined at 120 MPa. A remarkable destruction of starch granules was observed, and all the large granules disintegrated into irregular block-like structures after treatment at 120 MPa. Both crystalline and short-range ordered structure were progressively disrupted with the increase of pressure. The structural destruction was attributed to starch gelatinization, which depended on ISM pressure. ISM treatment could arbitrarily adjust pasting viscosity and increase setback value of potato starch. Moreover, moduli and mechanical rigidity of starch pastes were enhanced by ISM treatment. These results implied that ISM treatment could be a potential choice to modify starch containing large granules at an industrial level. Microfluidization was an available physical technique to improve functional properties of starch. However, it was difficult for conventional microfluidizer to treat starch containing big granule sizes both in laboratory and industrial scale owing to the drawbacks of devices. A recently designed "industry-scale microfluidizer" (ISM) in our laboratory could be applied to treat potato starch containing large granules. This preliminary study gave important indications that the practical industrial applications of potato starch could be widen by safe and simple microfludization technology, and ISM may be used for processing whole grains flour to obtain nutritional products. • Potato starch (PS) was treated by industry-scale microfluidizer (ISM). • ISM treatment disrupted granular, crystalline and short-range ordered structure of PS. • DSC confirmed higher degree of starch gelatinization due to more drastic treatment. • ISM induced-structural disturbance increased final viscosity and setback of PS. • ISM treatment enhanced elasticity and paste stability of PS. [ABSTRACT FROM AUTHOR]

A cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ is reported, which uses nonmetallic quinone DDQ as an oxidant in the allylation of N-benzylanilines under mild conditions. C–C bond with high selectivity and activity was constructed in this reaction and homoallylic amines were obtained with yields of up to 99%. Image 1 • DDQ-promoted allylation by using N-benzyl aniline as raw material, allyltributyltin as allyl reagent and DDQ as oxidant. • A series of N-benzyl anilines bearing a variety of functional groups such as halo, alkyl and cyano are scoped with yields of up to 99%. • This protocol presents a preparative scale synthesis and an alternative access to the concise synthesis of homoallylic amines. • The addition sequence of feed stocks and reaction mechanism are explored and interpreted rationally through NMR analysis. [ABSTRACT FROM AUTHOR]

Background: Inflammatory reaction in the dysfunction of retinal endotheliocytes has been considered to play a vital role in diabetic retinopathy (DR). Anti-inflammatory therapy so far gains poor outcome as DR treatment. This study aims to identify a novel therapeutic target of DR from the OMICs studies of a traditional anti-DR botanical products TNTL. Methods: Hyperglycemic mice were treated with TNTL. The anti-hyperglycemic effect of TNTL was validated to confirm the biological consistency of the herbal products from batches. Improvement of DR by TNTL was examined by various assays on the retina. Next-generation transcriptome sequencing and cytokine array was used to identify the therapeutic targets. In vitro study was performed to validate the target. Results: We observed that TNTL at its high doses possessed anti-hyperglycemic effect in murine type I diabetic model, while at its doses without reducing blood glucose, it suppressed DR incidence. TNTL restored the blood-retina barrier integrity, suppressed retinal neovascularization, and attenuated the retinal ganglion cell degeneration. Transcriptomic analysis on the retina tissue of hyperglycemic mice with or without TNTL revealed that the inflammatory retina microenvironment was significantly repressed. TNTL treatment suppressed pro-inflammatory macrophages in the retina, which resulted in the inactivation of endothelial cell migration, restoration of endothelial cell monolayer integrity, and prevention of leakage. Cytokine array analysis suggested that TNTL could significantly inhibit the secretion of MIP1γ from pro-inflammatory macrophages. Prevention of endothelial dysfunction by TNTL may be mediated by the inhibition of MIP1γ/CCR1 axis. More specifically, TNTL suppressed MIP1γ release from pro-inflammatory macrophages, which in turn inhibited the activation of CCR1-associated signaling pathways in endothelial cells. Conclusion: Our findings demonstrated that TNTL might be an alternative treatment to DR, and the primary source of potential drug candidates against DR targeting MIP1γ/CCR1 axis in the retinal microenvironment. [ABSTRACT FROM AUTHOR]