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• Scutellaria baicalensis ameliorates lower respiratory tract infection in mice. • Lower respiratory tract infections are related to respiratory microbiota dysbiosis. • Scutellaria baicalensis regulates IL-17A and GM-CSF in a microbiota-dependent manner. • Scutellaria baicalensis may target IL-17A and GM-CSF to resist infection in mice. • Scutellaria baicalensis modulates the respiratory microbiota in mice after infection. The pathogenesis of lower respiratory tract infections (LRTIs) has been demonstrated to be strongly associated with dysbiosis of respiratory microbiota. Scutellaria baicalensis , a traditional Chinese medicine, is widely used to treat respiratory infections. However, whether the therapeutic effect of S. baicalensis on LRTIs depends upon respiratory microbiota regulation is largely unclear. To investigate the potential effect and mechanism of S. baicalensis on the respiratory microbiota of LRTI mice. A mouse model of LRTI was established using Klebsiella pneumoniae or Streptococcus pneumoniae. Antibiotic treatment was administered, and transplantation of respiratory microbiota was performed to deplete the respiratory microbiota of mice and recover the destroyed microbial community, respectively. High-performance liquid chromatography (HPLC) was used to determine and quantify the chemical components of S. baicalensis water decoction (SBWD). Pathological changes in lung tissues and the expressions of serum inflammatory cytokines, including interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were determined by hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA), respectively. Quantitative real-time PCR (qRT-PCR) analysis was performed to detect the mRNA expression of GM-CSF. Metagenomic sequencing was performed to evaluate the effect of SBWD on the composition and function of the respiratory microbiota in LRTI mice. Seven main components, including scutellarin, baicalin, oroxylin A-7-O- β -d-glucuronide, wogonoside, baicalein, wogonin, and oroxylin A, were identified and their levels in SBWD were quantified. SBWD ameliorated pulmonary pathological injury and inflammatory responses in K. pneumoniae and S. pneumoniae -induced LRTI mice, as evidenced by the dose-dependent reductions in the levels of serum inflammatory cytokines, IL-6 and TNF-α. SBWD may exert a bidirectional regulatory effect on the host innate immune responses in LRTI mice and regulate the expressions of IL-17A and GM-CSF in a microbiota-dependent manner. K. pneumoniae infection but not S. pneumoniae infection led to dysbiosis in the respiratory microbiota, evident through disturbances in the taxonomic composition characterized by bacterial enrichment, including Proteobacteria, Enterobacteriaceae , and Klebsiella. K. pneumoniae and S. pneumoniae infection altered the bacterial functional profile of the respiratory microbiota, as indicated by increases in lipopolysaccharide biosynthesis, metabolic pathways, and carbohydrate metabolism. SBWD had a certain trend on the regulation of compositional disorders in the respiratory flora and modulated partial microbial functions embracing carbohydrate metabolism in K. pneumoniae -induced LRTI mice. SBWD may exert an anti-infection effect on LRTI by targeting IL-17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation. [Display omitted] [ABSTRACT FROM AUTHOR]

: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulate), a famous and characteristic Tibetan medicine, has been demonstrated to exert an outstanding brain protection role in the treatment of high-altitude hypoxia disease. However, the metabolic effects of R. crenulate on high-altitude hypoxic brain injury (HHBI) are still incompletely understood. Herein, the anti-hypoxic effect and associated mechanisms of R. crenulate were explored through both in vivo and in vitro experiments. The mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE, 0.5, 1.0 and 2.0 g/kg) and salidroside (Sal, 25, 50 and 100 mg/kg) was given by gavage for 7 days. Pathological changes and neuronal apoptosis of mice hippocampus and cortex were evaluated using H&E and TUNEL staining, respectively. The effects of RCE and Sal on the permeability of blood brain barrier (BBB) were detected by Evans blue staining and NIR-II fluorescence imaging. Meanwhile, the ultrastructural BBB and cerebrovascular damages were observed using a transmission electron microscope (TEM). The levels of tight junction proteins Claudin-1, ZO-1 and occludin were detected by immunofluorescence. Additionally, the metabolites in mice serum and brain were determined using UHPLC-MS and MALDI-MSI analysis. The cell viability of Sal on hypoxic HT22 cells induced by CoCl 2 was investigated by cell counting kit-8. The contents of LDH, MDA, SOD, GSH-PX and SDH were detected by using commercial biochemical kits. Meanwhile, intracellular ROS, Ca2+ and mitochondrial membrane potential were determined by corresponding specific labeled probes. The intracellular metabolites of HT22 cells were performed by the targeted metabolomics analysis of the Q300 kit. The cell apoptosis and necrosis were examined by YO-PRO-1/PI, Annexin V/PI and TUNEL staining. In addition, mitochondrial morphology was tested by Mito-tracker red with confocal microscopy and TEM. Real-time ATP production, oxygen consumption rate, and proton efflux rate were measured using a Seahorse analyzer. Subsequently, MCU, OPA1, p-Drp1ser616, p-AMPKα, p-AMPKβ and Sirt1 were determined by immunofluorescent and western blot analyses. The results demonstrated that R. crenulate and Sal exert anti-hypoxic brain protection from inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction protein Claudin-1, ZO-1 and occludin and improving mitochondrial morphology and function. Mechanistically, R. crenulate and Sal alleviated HHBI by enhancing the tricarboxylic acid cycle to meet the demand of energy of brain. Additionally, experiments in vitro confirmed that Sal could ameliorate the apoptosis of HT22 cells, improve mitochondrial morphology and energy metabolism by enhancing mitochondrial respiration and glycolysis. Meanwhile, Sal-mediated MCU inhibited the activation of Drp1 and enhanced the expression of OPA1 to maintain mitochondrial homeostasis, as well as activation of AMPK and Sirt1 to enhance ATP production. Collectively, the findings suggested that RCE and Sal may afford a protective intervention in HHBI through maintaining BBB integrity and improving energy metabolism via balancing MCU-mediated mitochondrial homeostasis by activating the AMPK/Sirt1 signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Salidroside (Sal), an active component from Rhodiola crenulata , has been confirmed to exert neuroprotective effects against hypoxia. However, its molecular mechanisms of intensifying mitochondrial function still largely unknown. In the present study, we aimed to explore the mechanisms by which Sal heightened mitochondrial function in CoCl 2 -induced HT22 hypoxic injury. The hypoxic condition of HT22 cells was performed by CoCl 2 stimulus. We then investigated the effects of Sal on the viability of hypoxic HT22 cells by cell counting kit-8. The contents of lactate dehydrogenase (LDH) release in cultured supernatant were detected by using commercial biochemical kit. Superoxide free radical scavenging activity, total antioxidant capacity assay kit with ferric reducing ability of plasma and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) methods were employed to detect the free radical scavenging ability and antioxidant capacity of Sal. Meanwhile, intracellular reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential (MMP) were determined by corresponding specific labeled probes. Mitochondrial morphology was tested by Mito-tracker green with confocal microscopy. Hoechst 33342 and Annexin V-FITC/propidium iodide staining were also employed to evaluate the effect of Sal on cell apoptosis. Oxygen consumption rate (OCR), real-time ATP production and proton efflux rate were measured using a Seahorse analyzer. Additionally, the potential interactions of Sal with PI3K-AKT signaling pathway-related proteins were predicted and tested by molecular docking, molecular dynamics simulation (MDS) and localized surface plasmon resonance (LSPR) techniques, respectively. Furthermore, the protein levels of p-PI3K, PI3K, p-AKT, AKT, p-JNK, JNK, p-p38 and p38 were estimated by western blot analysis. Sal alleviated CoCl2-induced hypoxic injury in HT22 cells as evidenced by increased cell viability and decreased LDH release. In vitro antioxidant test confirmed that Sal had marvelous antioxidant abilities. The protected mitochondrial function by Sal treatment was illustrated by the decrease of ROS, Ca2+, mitochondrial fragment and the increase of MMP. In addition, Sal ameliorated the apoptosis of HT22 cells by decreasing Hoechst 33342 positive cells and the rate of apoptotic cells. Enhancement of energy metabolism in HT22 by Sal was demonstrated by increased OCR, real-time ATP generation and proton efflux rate. The molecular docking confirmed the potential binding of Sal to PI3K, AKT and CaMK II proteins with calculated binding energy of -1.32, -4.21 and -4.38 kcal/mol, respectively. The MDS test revealed the average hydrogen bond of complex Sal-PI3K and Sal-AKT were 0.79 and 4.46, respectively. The results of LSPR verified the potential binding of Sal to proteins PI3K, AKT and HIF-1α with affinity values of 5.20 × 10 − 3, 2.83 × 10 − 3 and 3.97 × 10 − 3 KD, respectively. Western blot analysis further argued that Sal consolidated the levels of p-PI3K and p-AKT. Meanwhile, Sal could downregulate the proteins expression of p-JNK and p-p38. Collectively, our findings suggested that Sal can intensify mitochondrial function of CoCl2-simulated hypoxia injury in HT22 cells by stimulating PI3K-AKT-MAPK signaling pathway. Sal is a potential agent for mitochondrial protection against hypoxia with the underlying molecular mechanisms of energy metabolism being further elucidated. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease that often results in joint destruction. Ershiwuwei Lvxue Pill (ELP), a prescription of Tibetan medicine, has been used for centuries for the clinical treatment of RA in Tibet, China. In a previous study, we reported that ELP could ameliorate RA symptoms in CIA rats by inhibiting the inflammatory response and inducing apoptosis in synovial tissues. It is still needed further to clarify the mechanisms of action of ELP in mitigating RA.Purpose: In this study, we aim to elucidate the mechanism of action of ELP to improve RA joint damage and explore the changes in the intestinal flora and host metabolites.Methods: Firstly, we analyzed the main absorbed constituents of ELP in the serum of rats by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF/MS). Then, we verified the alleviating effects of ELP on cartilage injury and bone erosion as well as the inflammatory response in CIA rats by microCT, H&E staining, safranin-O staining, and ELISA. Moreover, we investigated the main factors that mediate joint damage, including the production of matrix metalloproteinases (MMPs) and osteoclast activity in the ankle of rats by immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining. Further, we explored the molecular mechanisms of the MMPs production and osteoclast activity in CIA rats treated with ELP through various experiments such as ELISA, qRT-PCR, western blotting, and immunofluorescence assay. Besides, we investigated gut microbiota composition by 16S rDNA sequencing and serum metabolites through untargeted metabolomics. In addition, we analyzed the correlation between gut microbiota and metabolites by Spearman correlation analysis.Results: In this study, we identified 20 compounds from rat serum samples, which could be the ELP components that improve RA. Moreover, we found that ELP could alleviate cartilage and bone injury by reducing MMP-1, MMP-3, and MMP-13 expression and osteoclast activity in CIA rats. Further studies demonstrated that ELP could reduce joint damage by inhibiting osteoprotegerin (OPG)/receptor activator for nuclear factor-κB ligand (RANKL) /nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinases (JNK) signal pathways. The 16S rDNA sequencing analysis indicated that there was a significant difference in the gut microbiota composition between the normal and CIA rats, and these differences were changed after ELP administration. ELP could alter the gut microbiota by increasing the abundance of the genus Lactobacillus and decreasing the abundance of Dorea, [Eubacterium]_ventriosum_group, Anaerostipes, Collinsella, Coprococcus_1, Ruminiclostridium_5, Ruminococcus_1, Family_XIII_UCG-001, Butyricicoccus, Erysipelotrichaceae_UCG-003, Lachnoclostridium, Faecalibacterium, Lachnospiraceae_UCG-010, Roseburia, Rs-E47_termite_group_norank, Treponema_2 genera. Non-targeted metabolomics analysis showed that ELP reduced arachidonic acid levels. The serum arachidonic acid level was significantly correlated with the abundance of 41 genera, particularly Collinsella and Lactobacillus.Conclusion: Our study shows that ELP can improve RA joint damage by inhibiting MMPs production and osteoclast activity, and regulating intestinal flora and host metabolites, which provides a novel insight into the ELP in alleviating RA. [ABSTRACT FROM AUTHOR]

Background: Rhodiola crenulate (R. crenulate), a famous Tibetan medicine, has been demonstrated to possess superiorly protective effects in high-altitude hypoxic brain injury (HHBI). However, its mechanisms on HHBI are still largely unknown.Methods: Herein, the protective effects and underlying mechanisms of R. crenulate on HHBI of BABL/c mice were explored through in vivo experiments. The mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE) (0.5, 1.0 and 2.0 g/kg) was given by gavage for 7 days. Pathological changes and neuronal viability of mice hippocampus and cortex were evaluated using H&E and Nissl staining, respectively. The brain water content (BWC) in mice was determined by calculating the ratio of dry to wet weight of brain tissue. And serum of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH-Px) and lactate dehydrogenase (LDH) were detected via commercial biochemical kits. Synchronously, the contents of total antioxidant capacity (T-AOC), lactic acid (LA), adenosine triphosphate (ATP), succinate dehydrogenase (SDH), pyruvate kinase (PK), Ca2+-Mg2+-ATPcase, Na+-K+-ATPcase, TNF-α, IL-1β and IL-6 in brain tissue were quantitative analysis by corresponding ELISA assay. Subsequently, NLRP3, ZO-1, claudin-5, occluding, p-p65, p65, ASC, cleaved-caspase-1, caspase-1 and IL-18 were determined by immunofluorescent and western blot analyses.Results: The results demonstrated that RCE remarkably alleviated pathological damage, BWC, as well enhanced neuronal viability. Furthermore, the oxidative stress injuries were reversely abrogated after RCE treatment, evidenced by the increases of SOD, GSH-Px and T-AOC, while the decreases of MDA and LDH contents. Marvelously, the administration of RCE rectified and balanced the abnormal energy metabolism via elevating the levels of ATP, SDH, PK, Ca2+-Mg2+-ATPcase and Na+-K+-ATPcase, and lowering LA. Simultaneously, the expression of tight junction proteins (ZO-1, claudin-5 and occludin) was enhanced, illustrating RCE treatment might maintain the integrity of blood-brain barrier (BBB). Additionally, RCE treatment confined the contents of IL-6, IL-1β and TNF-α, and attenuated fluorescent signal of NLRP3 protein. Concurrently, the results of western blot indicated that RCE treatment dramatically restrained p-p65/p65, ASC, NLRP3, cleaved-caspase-1/caspase-1 and IL-18 protein expressions in brain tissues of mice.Conclusion: RCE may afford a protectively intervention in HHBI of mice through suppressing the oxidative stress, improving energy metabolism and the integrity of BBB, and subsiding inflammatory responses via the NF-κB/NLRP3 signaling pathway. As a promising agent for the treatment of mice HHBI, the deep-crossing molecular mechanisms of R. crenulate still needs to be further elucidated to identify novel core hub targets. [ABSTRACT FROM AUTHOR]

Background: Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) and mainly develops from long-term intestinal inflammation. Mounting evidence reveals that activated Hedgehog signaling pathway plays a vital role in the pathogenesis of CRC. Scutellarin is a type of phytochemical flavonoid with a powerful efficacy on various malignancies, including CRC.Aim: Here, we studied the therapeutic effect of scutellarin on CRC and its direct regulating targets.Methods: The CAC model in mice was established by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by detection of the efficacies of scutellarin on the carcinogenesis, apoptosis, inflammation, Hedgehog signaling cascade and complicated inflammatory networks in CAC tissues of mice. In CRC SW480 cells, the effects of scutellarin on malignant phenotype, apoptosis and Hedgehog signaling were examined. In TNF-α-stimulated IEC-6 intestinal epithelial cells, the actions of scutellarin on inflammatory response and Hedgehog signals were assessed as well.Results: Scutellarin significantly ameliorated AOM/DSS-caused CAC in mice and induced apoptosis in CAC tissues of mice, by inhibiting NF-κB (nuclear factor kappa B) -mediated inflammation and Hedgehog signaling axis. RNA-seq and transcriptome analysis indicated that scutellarin regulated complicated inflammatory networks in mouse CAC. Also, scutellarin suppressed the proliferation, migration, colony formation, and induced apoptosis of SW480 cells by down-regulation of Hedgehog signaling pathway activity. Additionally, scutellarin lessened NF-κB-mediated inflammatory response in TNF-α-stimulated IEC-6 cells, by attenuating Hedgehog signaling cascade.Conclusion: Scutellarin potently ameliorates CAC by suppressing Hedgehog signaling pathway activity, underpinning the promising application of scutellarin to CRC in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Globally, lung cancer is the leading cause of cancer associated mortalities. The current conventional chemotherapy remains the preferred treatment option for lung cancer, as surgical resection plays little role in the treatment of over 75% of lung cancer patients. Therefore, there is a need to develop novel potential therapeutic drugs or adjuvants with a high efficiency and safety against lung cancer. Scutellaria baicalensis Georgi, a common Chinese medicinal herb that has been in use for more than 2000 years, has recently been shown to possess significant activities against lung cancer. However, current research progress on pharmacological effects and relevant molecular mechanisms of S. baicalensis in lung cancer therapy have not been systematically summarized.Purpose: This review aimed at elucidating on the anti-lung cancer mechanisms and antitumor efficacies of S. baicalensis as well as its active ingredients, and providing a valuable reference for further investigation in this field.Methods: We used "Scutellaria baicalensis" or the name of the compound in S. baicalensis, in combination with "lung cancer" as key words to systematically search for relevant literature from the Web of Science and PubMed databases. Publications that investigated molecular mechanisms were the only ones selected for analysis. The PRISMA guidelines were followed.Results: Fifty-four publications met the inclusion criteria for this study. Five anti-lung cancer mechanisms of S. baicalensis and its constituent components are discussed. These mechanisms include apoptosis induction, cell-cycle arrest, suppression of proliferation, blockade of invasion and metastasis, and overcoming drug-resistance. These compounds exhibited high antitumor efficacies and safety against lung cancer xenografts.Conclusion: Studies should aim at elucidating on the anti-cancer mechanisms of S. baicalensis to achieve the ultimate goal of lung cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Shikonin is one of the major phytochemical components of Lithospermum erythrorhizon (Purple Cromwell), which is a type of medicinal herb broadly utilized in traditional Chinese medicine. It is well established that shikonin possesses remarkable therapeutic actions on various diseases, with the underlying mechanisms, pharmacokinetics and toxicological effects elusive. Also, the clinical trial and pharmaceutical study of shikonin remain to be comprehensively delineated.Purpose: The present review aimed to systematically summarize the updated knowledge regarding the therapeutic actions, pharmacokinetics, toxicological effects, clinical trial and pharmaceutical study of shikonin.Methods: The information contained in this review article were retrieved from some authoritative databases including Web of Science, PubMed, Google scholar, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database and so on, till August 2021.Results: Shikonin exerts multiple therapeutic efficacies, such as anti-inflammation, anti-cancer, cardiovascular protection, anti-microbiomes, analgesia, anti-obesity, brain protection, and so on, mainly by regulating the NF-κB, PI3K/Akt/MAPKs, Akt/mTOR, TGF-β, GSK3β, TLR4/Akt signaling pathways, NLRP3 inflammasome, reactive oxygen stress, Bax/Bcl-2, etc. In terms of pharmacokinetics, shikonin has an unfavorable oral bioavailability, 64.6% of the binding rate of plasma protein, and enhances some metabolic enzymes, particularly including cytochrome P450. In regard to the toxicological effects, shikonin may potentially cause nephrotoxicity and skin allergy. The above pharmacodynamics and pharmacokinetics of shikonin have been validated by few clinical trials. In addition, pharmaceutical innovation of shikonin with novel drug delivery system such as nanoparticles, liposomes, microemulsions, nanogel, cyclodextrin complexes, micelles and polymers are beneficial to the development of shikonin-based drugs.Conclusions: Shikonin is a promising phytochemical for drug candidates. Extensive and intensive explorations on shikonin are warranted to expedite the utilization of shikonin-based drugs in the clinical setting. [ABSTRACT FROM AUTHOR]

Scutellarin (Scu), a flavonoid from herbal Erigeron breviscapus (Vaniot) Hand-Mazz, exerts neuroprotective effects against cerebral ischemia. However, whether the effects of Scu are related to mitochondrial protection needs further investigation. In this study, we aimed to clarify the mechanisms of Scu against HT22 cells injury caused by oxygen-glucose deprivation and reperfusion (OGD/R). Our results proved that Scu significantly reduced the overload of intracellular reactive oxygen species (cellar ROS) and mitochondria reactive oxygen species (mito-ROS), ameliorating oxidative stress damage. TUNEL positive rate, Caspase-3 activity, and Cytochrome c (Cyto-c) expression remarkably decreased following Scu treatment. Meanwhile, Scu could maintain mitochondrial morphology and reverse ultrastructure changes. And mitochondrial membrane potential (MMP), oxygen consumption rate (OCR), adenosine triphosphate (ATP) production and Na+/K+-ATPase activity were obviously promoted. Additionally, Scu was found to stimulate mitophagy level by increasing the expression of LC3, Beclin1, PINK1 and Parkin proteins, as well as promoting the degradation of p62. More importantly, the regulatory effects of Scu on mito-ROS, MMP, ATP, Na+/K+-ATPase, cell viability and lactate dehydrogenase (LDH) were markedly limited by Mdivi-1 (a mitophagy inhibitor). Of note, the inhibitor also reversed Scu-mediated apoptosis suppression, evidenced by the diminished apoptosis rate, the down-regulated expression activities of Cyto-c, Bax and cleaved Caspase-3, as well as the elevated level of Bcl-2 protein. Collectively, Scu could improve mitochondrial dysfunction and inhibit apoptosis by stimulating mitophagy, thereby attenuating OGD/R-induced HT22 cells injury. [Display omitted] • Scu displays neuroprotection by maintaining mitochondrial integrity and improving mitochondrial energy metabolism. • Scu can alleviate mitochondrial dysfunction and apoptosis through mitophagy induction. • Scu is expected to be a promising agent for mitochondrial protection against cerebral ischemia. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Rheum rhabarbarum (rhubarb) has long been used for the treatment of inflammation in China and other Asian countries. However, the mechanism underlying the anti-inflammatory activity of this medicinal plant is not fully understood. The present study was designed to investigate the anti-inflammatory effects of anthraquinones, the major constituents in rhubarb, and the molecular mechanism involved in their anti-inflammatory effects. Materials and methods: RAW264.7 cells were stimulated by lipopolysaccharide (LPS) in the presence or absence of the compounds examined. The proliferation of RAW264.7 cells was assayed by the Alamar-Blue method. The quantity of nitric oxide (NO) was determined by Griess assay. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. Inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor ?B? (I?B?), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), and Akt/phosphoinositide 3-kinase (PI3K) protein expression levels were determined by Western blotting. Results: Aloe-emodin markedly suppressed the production of NO, interleukin-6 (IL-6), and interleukin-1? (IL-1?) in LPS-stimulated RAW264.7 cells with no apparent cytotoxicity. The mRNA expression levels of iNOS, IL-6, and IL-1? genes were also significantly inhibited by aloe-emodin. Western blot analysis showed that aloe-emodin suppressed LPS-induced iNOS protein expression, I?B? degradation, and the phosphorylation of ERK, p38, JNK, and Akt. Conclusions: These results demonstrate that aloe-emodin is the bioactive component of rhubarb that confers an anti-inflammatory effect through a likely mechanism involving a decrease in pro-inflammatory cytokine production in LPS-induced RAW264.7 macrophages via inhibition of NF-?B, MAPK, and PI3K pathways. [Copyright &y& Elsevier]

As a component of nutraceuticals, dietary fibers (DFs) are essential for maintain human growth and health via the regulation of gut microbiota in the digestive tract. In this review, we summarize food-derived DFs and their effect on gut microbiota-derived short-chain fatty acids (SCFAs). DFs accelerate the production of SCFAs mainly by stimulating intestinal Lactobacillus , Bifidobacterium and Akkermansia to treat diabetes, obesity, cancer, inflammation and immunodeficiency. Further studies should focus on clarifying the detailed mechanism between DFs and diseases associated with gut microbiota-mediated SCFAs. [ABSTRACT FROM AUTHOR]

Lonicerae japonicae flos (LJF), known as Jin Yin Hua in Chinese, is one of the most commonly used traditional Chinese herbs and nutraceuticals. Nowadays, LJF is broadly applied in an array of afflictions, such as fever, sore throat, flu infection, cough, and arthritis, with the action mechanism to be elucidated. Here, we strove to summarize the main phytochemical components of LJF and review its updated pharmacological effects, including inhibition of inflammation, pyrexia, viruses, and bacteria, immunoregulation, and protection of the liver, nervous system, and heart, with a focus on the potential efficacy of LJF on coronavirus disease–2019 based on network pharmacology so as to fully underpin the utilization of LJF as a medicinal herb and a favorable nutraceutical in daily life. [ABSTRACT FROM AUTHOR]

The highlands evoke both fascination and awe. Regardless of the reason to live in the highlands, symptoms related to altitude sickness are unbearable because of low atmospheric pressure, low oxygen concentration, strong ultraviolet radiation, cold, and psychological factors. Food and herbal medicines and/or health-care foods have protected highland dwellers owing to their multisystem regulation. These versatile products combine health-care properties with medical values by enhancing immunity, relieving physical fatigue, improving sleep, and augmenting hypoxia tolerance, with rare side effects. We therefore aimed to provide a more comprehensive analysis of these nutraceuticals, which can be used to prevent and treat symptoms of altitude hypoxia in the Chinese market. Finally, we dissect a new perspective for their promotion and development from molecular aspects. [ABSTRACT FROM AUTHOR]

Cycads, which primarily consist of the families Cycadaceae and Zamiaceae, possess intrinsic therapeutic attributes that are prominently expressed across their morphological spectrum, including roots, leaves, flowers, and seeds. In Chinese traditional medicine, the leaves of cycads are particularly revered for their profound healing capabilities. This meticulous review engages with existing literature on cycads and presents insightful avenues for future research. Over 210 phytoconstituents have been isolated and identified from various cycad tissues, including flavonoids, azoxy metabolites, sterols, lignans, non-proteogenic amino acids, terpenoids, and other organic constituents. The contemporary pharmacological discourse highlights the antineoplastic, antimicrobial, and antidiabetic activities inherent in these ancient plants, which are of particular importance to the field of oncology. Despite the prevalent focus on crude extracts and total flavonoid content, our understanding of the nuanced pharmacodynamics of cycads lags considerably behind. The notoriety of cycads derived toxicity, notably within the context of Guam's neurological disease cluster, has precipitated an established emphasis on toxicological research within this field. As such, this critical review emphasizes nascent domains deserving of academic and clinical pursuit, whilst nested within the broader matrix of current scientific understanding. The systematic taxonomy, traditional applications, phytochemical composition, therapeutic potential, and safety profile of cycads are holistically interrogated, assimilating an indispensable repository for future scholarly inquiries. In conclusion, cycads stand as a veritable treasure trove of pharmacological virtue, displaying remarkable therapeutic prowess and holding vast promise for ongoing scientific discovery and clinical utilization. Cycads represent a rich, therapeutic resource, exhibiting exceptional medicinal efficacy and enormous potential for continued exploration and application. [Display omitted] • Up to now, more than 210 phytochemicals have been identified from cycads. • Cycads is a double-edged sword, and its toxicity should not be overlooked. • Cycads has great medical development and application value. [ABSTRACT FROM AUTHOR]

The load distribution of balls is the key to affect the gradual wear and the life of the ball screw. Because the structure of ball screw mechanism is complex and closed, it is difficult to experimentally determine the contact loads of balls between the nut and the screw. This paper presents a novel method to analyze the static load distribution of ball screws, which takes into account the nut position variation. In order to investigate the load distribution conveniently, an appropriate transformation coordinate system is established. The axial, torsional and lateral elastic deformations are comprised into the geometric relationship of the groove centers of the screw and the nut by representing the ball screw as beam elements. The nonlinear equations, which take into account the Hertzian contact deformation, are solved iteratively by using the Newton-Raphson numerical method to determine the contact load of each ball. The detailed analysis for the distribution of contact load, contact angle and torsion angle when the nut is located at different positions of the screw. Furthermore, the effects of axial load and original contact angle on load distribution are analyzed. [ABSTRACT FROM AUTHOR]

Microfluidic chip (MC) has helped more researchers to perform labs on a chip, with the advantages of precise control, lower sample requirement and reagent consumption, economic efficiency and high throughput screening. Its combination with other technologies, such as biosensor technology, mass spectrometry, and automated imaging systems, has emerged as a novel platform for model construction of multidimensional cells and organs, identification of multiple disease markers, and screening of drugs and metabolites. Specifically, the MC is increasingly employed to detect autophagy–associated markers in vitro. This review summarizes the development history of major technological innovations of MC, application fields, conventional methods and shortcomings for autophagy detection, as well as the application of MC in autophagy detection. Finally, we discuss the current technical challenges, and possible innovations in the diagnosis of autophagy–related diseases in the future. Image 1 • MC integrates biosensor technology, mass spectrum and automated imaging systems into a rounded system. • Advantages of the MC include rapid analysis, high integration, high precision, high imitation simulation, high-throughput and miniaturization. • Best detection and analysis for autophagy–related markers are described. [ABSTRACT FROM AUTHOR]

Near-infrared II (NIR-II) functional dyes can diagnose various diseases in non-invasive conditions. Dynamic visualization of ischemic stroke has the potential to expedite stroke diagnosis and facilitates timely treatment to alleviate cerebral injury in the continuum of stroke care. However, there is still a lack of effective imaging methods to visualize the infarct area of ischemic stroke. In this study, we report a near-infrared II (NIR-II, 1–1.7 μm) fluorophore HLX with the unique twisted donor-acceptor π-architecture, which exhibits strong aggregation induced emission characteristics and high fluorescence quantum yield in the NIR-II window and near-infrared IIb (NIR-IIb, 1.5–1.7 μm) region. The whole-body vascular imaging with superior clarity using HLX dots was achieved. Most importantly, HLX dots was utilized to realize NIR-IIb fluorescence imaging of ischemic stroke in animals and dynamically monitor the therapeutic efficacy of salidroside for the first time. Our studies further demonstrate the neuroprotective effects of salidroside against cerebral ischemic injury through promoting angiogenesis. Superior biocompatibility enables HLX as a potential agent in the NIR-IIb region to light up the infarcted vessels and image-guided therapy of ischemic stroke. [Display omitted] • A near-infrared II functional dye HLX is synthesized with strong aggregation induced emission characteristics and high fluorescence quantum. • The whole-body vascular imaging with superior clarity using HLX dots was achieved. • HLX dots was utilized to dynamically monitor the ischemic stroke therapeutic efficacy of salidroside for the first time. [ABSTRACT FROM AUTHOR]