Integration of pharmacodynamics and metabolomics to reveal rhubarb anthraquinone protection against nonalcoholic fatty liver disease rat model.

OBJECTIVES: The objective of the present study was to investigate the effect of Rhubarb anthraquinone (RA) on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) rat model, and explore potential biomarker and metabolic pathways by using the metabolomics method. MATERIALS AND METHODS: We established HFD rats as the NAFLD model. Forty Sprague-Dawley rats were randomly divided into a control group, model group, RA low-dose group, RA medium-dose group, and RA high-dose group, and evaluated the protective effect of RA on NAFLD by detecting biochemical indicators of serum and pathological changes of liver tissue. Investigating potential biomarkers and metabolic pathways connected with RA's protective effects against NAFLD by UHPLC-Q-TOF-MS untargeted metabolomics. RESULTS: The results showed that RA significantly reversed the increase of TG, TC, ALT, AST, and ALP (P < .05), the decrease of HDL-C (P < .05), and alleviated pathological conditions in NAFLD rats. Based on potential biomarker analysis, RA affected metabolic pathways such as fatty acids biosynthesis, bile acids biosynthesis, and pentose phosphate pathway, delaying the progression of NAFLD. CONCLUSION: RA improved blood lipid levels, liver function, and pathological conditions of NAFLD rats. Meanwhile, affected the metabolic pathways and regulated the synthesis of fatty acids and bile acids in NAFLD rats.

Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. METHODS: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. RESULTS: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. CONCLUSIONS: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. TRIAL REGISTRATION: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.

Protective mechanism of Paeonol on central nervous system.

Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.

Integrative transcriptomic and metabolomic analyses reveal the phenylpropanoid and flavonoid biosynthesis of Prunus mume.

Prunus mume is an important medicinal plant with ornamental and edible value. Its flowers contain phenylpropanoids, flavonoids and other active components, that have important medicinal and edible value, yet their molecular regulatory mechanisms in P. mume remain unclear. In this study, the content of total flavonoid and total phenylpropanoid of P. mume at different developmental periods was measured first, and the results showed that the content of total flavonoid and total phenylpropanoid gradually decreased in three developmental periods. Then, an integrated analysis of transcriptome and metabolome was conducted on three developmental periods of P. mume to investigate the law of synthetic accumulation for P. mume metabolites, and the key enzyme genes for the biosynthesis of phenylpropanoids and flavonoids were screened out according to the differentially expressed genes (DEGs). A total of 14,332 DEGs and 38 differentially accumulate metabolites (DAMs) were obtained by transcriptomics and metabolomics analysis. The key enzyme genes and metabolites in the bud (HL) were significantly different from those in the half-opening (BK) and full-opening (QK) periods. In the phenylpropanoid and flavonoid biosynthesis pathway, the ion abundance of chlorogenic acid, naringenin, kaempferol, isoquercitrin, rutin and other metabolites decreased with the development of flowers, while the ion abundance of cinnamic acid increased. Key enzyme genes such as HCT, CCR, COMT, CHS, F3H, and FLS positively regulate the downstream metabolites, while PAL, C4H, and 4CL negatively regulate the downstream metabolites. Moreover, the key genes FLS (CL4312-2, CL4312-3, CL4312-4, CL4312-5, CL4312-6) regulating the synthesis of flavonols are highly expressed in bud samples. The dynamic changes of these metabolites were validated by determining the content of 14 phenylpropanoids and flavonoids in P. mume at different developmental periods, and the transcription expression levels of these genes were validated by real-time PCR. Our study provides new insights into the molecular mechanism of phenylpropanoid and flavonoid accumulation in P. mume.

Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. AIM OF THE STUDY: The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. METHODS: First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. RESULTS: A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. CONCLUSION: By combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.

Rapid detection of ash content in black tea using a homemade miniature near-infrared spectroscopy.

Ash is a testing index with both health inspection value and quality decision value, and it is an essential detection item in the import and export trade of tea. To realize the rapid and effective quantitative analysis of ash content in tea, this study proposed the use of a homemade miniature near-infrared (NIR) spectroscopy combined with multivariate analysis for the rapid detection of ash content in black tea. First, NIR data of black tea samples from different countries were acquired and optimized by the spectral preprocessing method. Then, the optimized pre-processed spectral data were used as features, and four feature wavelength selection algorithms, such as competitive adaptive reweighted sampling, iteratively retaining informative variables (IRIV), variable combination population analysis (VCPA)-IRIV, and interval variable iterative space shrinkage approach (IVISSA), were utilized to optimize the feature spectra. Finally, the support vector machine regression (SVR) algorithm was employed to construct the quantitative models of ash content in black tea by combining the optimal wavelengths obtained from the four feature selection methods mentioned above. The experimental results showed that the IVISSA-SVR model had the best performance, with correlation coefficient (Rp), root mean square errors of prediction (RMSEP), and relative prediction deviation (RPD) of 0.9546, 0.0192, and 5.59 for the prediction set, respectively. The results demonstrate that a miniature NIR sensing system combined with chemometrics as an effective analytical tool can realize the rapid detection of ash content in black tea.

Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats.

BACKGROUND AND OBJECTIVES: Rhubarb anthraquinones contain five main components, that is, rhein, emodin, aloe-emodin, chrysophanol, and physcion, which demonstrate good therapeutic effects on nonalcoholic fatty liver disease (NAFLD). However, research on its pharmacokinetics in NAFLD remains lacking. This study aimed to investigate the pharmacokinetic differences of rhubarb anthraquinones in normal and NAFLD rats. METHODS: This study developed an NAFLD rat model by high-fat diet feeding for 6 weeks. Normal and NAFLD groups were orally administered different rhubarb anthraquinones doses (37.5, 75, and 150 mg/kg). The concentration of the rhein, emodin, aloe-emodin, chrysophanol, and physcion in plasma was determined by high-performance liquid chromatography-ultraviolet. RESULTS: The results revealed significant differences in pharmacokinetic behavior between normal and NAFLD rats. Compared with normal rats, NAFLD rats demonstrated significantly increased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0 → ∞) of rhubarb anthraquinones (P < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (Tmax), terminal elimination half-life (t1/2), and mean residence time (MRT) of rhubarb anthraquinones (P < 0.05). CONCLUSIONS: This study indicates significant differences in the pharmacokinetics of rhubarb anthraquinones between the physiological and NAFLD states of rats. Rhubarb anthraquinone demonstrated a longer retention time and slower absorption rate in NAFLD rats and exhibited higher bioavailability and peak concentration. This finding provides important information for guiding the clinical use of rhubarb anthraquinones under pathological conditions.

Piper nigrum Extract Inhibits the Growth of Human Colorectal Cancer HT-29 Cells by Inducing p53-Mediated Apoptosis.

Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract with the second highest mortality rate globally. Piper nigrum is a widely used traditional medicinal plant, exhibiting antitumor activity against various tumor cells. At present, research on the effect of Piper nigrum on CRC is limited to in vitro cytotoxicity, lacking comprehensive mechanism investigations. This study aimed to explore the inhibitory effect and mechanism of Piper nigrum extract (PNE) on HT-29 cells. Firstly, we identified the chemical components of PNE. Then, MTT assay, colony formation assay, JC-1 staining, and flow cytometry were used to analyze the effect of PNE on HT-29 cells in vitro. A xenograft model, histopathological examination, immunohistochemistry, and western blot were used to evaluate the tumor growth inhibitory activity and mechanism of PNE in vivo. The results indicated that PNE could inhibit cell proliferation and colony formation, reduce mitochondrial membrane potential, induce cell apoptosis in vitro, and inhibit tumor growth in vivo. Furthermore, PNE could regulate p53 and its downstream proteins, and subsequently activate the caspase-3 pathway. In summary, PNE probably induced apoptosis of HT-29 cells through the mitochondrial pathway mediated by p53. All these results suggested that PNE might be a potential natural-origin anti-CRC drug candidate.

A comprehensive review on pharmacological, toxicity, and pharmacokinetic properties of phillygenin: Current landscape and future perspectives.

Forsythiae Fructus is a traditional Chinese medicine frequently in clinics. It is extensive in the treatment of various inflammation-related diseases and is renowned as 'the holy medicine of sores'. Phillygenin (C21H24O6, PHI) is a component of lignan that has been extracted from Forsythiae Fructus and exhibits notable biological activity. Modern pharmacological studies have confirmed that PHI demonstrates significant activities in the treatment of various diseases, including inflammatory diseases, liver diseases, cancer, bacterial infection and virus infection. Therefore, this review comprehensively summarizes the pharmacological effects of PHI up to June 2023 by searching PubMed, Web of Science, Science Direct, CNKI, and SciFinder databases. According to the data, PHI shows remarkable anti-inflammatory, antioxidant, hepatoprotective, antitumour, antibacterial, antiviral, immunoregulatory, analgesic, antihypertensive and vasodilatory activities. More importantly, NF-κB, MAPK, PI3K/AKT, P2X7R/NLRP3, Nrf2-ARE, JAK/STAT, Ca2+-calcineurin-TFEB, TGF-ß/Smads, Notch1 and AMPK/ERK/NF-κB signaling pathways are considered as important molecular targets for PHI to exert these pharmacological activities. Studies of its toxicity and pharmacokinetic properties have shown that PHI has very low toxicity, incomplete absorption in vivo and low oral bioavailability. In addition, the physico-chemical properties, new formulations, derivatives and existing challenges and prospects of PHI are also reviewed and discussed in this paper, aiming to provide direction and rationale for the further development and clinical application of PHI.

Essential oil from Artemisia argyi alleviated liver disease in zebrafish (Danio rerio) via the gut-liver axis.

The popularity of intensive fish farming has led to the emergence of fish diseases characterized by hepatobiliary syndrome. Artemisia argyi (A. argyi) essential oils have anti-inflammatory and anti-oxidant effects. However, their alleviating effects and mechanism on liver disease in fish are still unclear. Thus, adult zebrafish were used to construct an animal model to observe histopathological damages, determine biochemical parameters and expression of inflammatory cytokines and mRNAs in the PPAR-γ/NF-κB pathway, and conduct 16 S sequencing of intestinal microbiota. The results found that after treatment with A. argyi essential oil, the histopathological damage caused by ethanol was relieved; the CAT, SOD, and GSH levels were remarkably elevated, while the MDA level was obviously lowered (P < 0.05); the expression levels of IL-10 and IFN-γ mRNAs were enhanced, but the levels of IL-1ß, IL-6, PPAR-γ, NF-κB, and TNF-α mRNAs were reduced (P < 0.05) relative to the EtOH group. A. argyi essential oil remarkably attenuated the damage to intestinal tissue structure, and elevated the levels of Muc2, ZO-1, Claudin-1, and Occludin mRNA (P < 0.05). Sequencing of the gut flora showed that A. argyi essential oil significantly altered the composition of gut microbes compared with the EtOH group. In addition, KEGG and COG analyses also showed significant (P < 0.05) changes in acetate cycling metabolism in the EtOH group, catechol 2, 3-dioxygenase and nitroreductase were significantly increased (P < 0.001), and lipid metabolism and terpenoid synthesis were significantly elevated (P < 0.001) in A. argyi essential oil group. The results indicate that A. argyi essential oil could effectively relieve ethanol-caused histopathological damage of livers by modulating the composition of gut microbiota, thus inhibiting the level of IL-1ß and mRNAs in the PPAR-γ/NF-κB pathway, increasing the IL-10 level, reducing the oxidative stress. This may offer a rationale for further research on the rationality of A. argyi as a substitute for feed antibiotics in aquaculture.

[Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway].

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-ß1(TGF-ß1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-ß1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

Aurantio-obtusin ameliorates obesity by activating PPARα-dependent mitochondrial thermogenesis in brown adipose tissues.

Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.

[Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging].

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.

Ethanol extract of Piper wallichii ameliorates DSS-induced ulcerative colitis in mice: Involvement of TLR4/NF-κB/COX-2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper wallichii (family: Piperaceae), a folk herbal medicine with anti-inflammatory and anti-thrombotic properties, has been traditionally used to treat rheumatic arthralgia, lumbocrural pain, gastrointestinal flatulence, and other intestinal diseases in China, Thailand, and India. However, there is no scientific report on the efficacy and potential mechanisms of Piper wallichii for ulcerative colitis (UC). AIM OF THE STUDY: The study aims to investigate the therapeutic effect and possible molecular mechanisms of the ethanol extract of Piper wallichii (EEPW) on DSS-induced UC in BALB/c mice. MATERIALS AND METHODS: The main components in EEPW were characterized by UPLC-QE-Orbitrap-MS. Subsequently, the anti-inflammatory effect of EEPW in vitro was preliminarily evaluated in RAW264.7 cells stimulated with LPS. UC model mice were triggered by free access to 4% DSS aqueous solution for 12 consecutive days, and simultaneously, EEPW (25, 50, and 100 mg/kg) and tofacitinib (positive control, 30 mg/kg) were orally administrated, respectively. The therapeutic efficacy of EEPW on UC was assessed by body weight, DAI, colon length, and pathological morphology. Besides, we investigated the effects of EEPW on intestinal barrier function, inflammatory factors, and immune systems of UC mice through immunohistochemistry (IHC), flow cytometry, and other techniques. Moreover, the expression of related proteins in the TLR4/NF-κB/COX-2 pathway was analyzed by Western blot. RESULTS: A total of 14 components were identified in the positive and negative modes, including isofutoquinol A (11), hancinone C (12), and futoquinol (14) which characterized by references. In the RAW264.7 cells experiments, the extract significantly suppressed the levels of TNF-α and IL-6. More importantly, EEPW distinctly improved the symptoms of DSS-induced UC mice as reflected by a significant recovery from body weight, colon length, pathological injuries of the colon, and so on. Further research found that EEPW remarkably restored the levels of occludin, promoted proliferation, and inhibited apoptosis in colon to maintain the integrity of intestinal barrier. In addition, the down-regulation of TNF-α and IL-1ß in colon, Th1 and Th17 cells in spleen, as well as the up-regulation of IL-10 in colon and Th2 cells in spleen were distinctly observed in EEPW-treated groups. Furthermore, the protein expression of TLR4, p-IκB-α, p-p65, and COX-2 were significantly inhibited by EEPW. CONCLUSIONS: This study confirmed for the first time that EEPW effectively ameliorated DSS-induced UC in mice, which might be related to improving intestinal barrier function, maintaining the levels of inflammatory factors, and regulating the immune system. In addition, we found that the anti-inflammatory effect of EEPW on UC mice was involved in the TLR4/NF-κB/COX-2 signaling pathway. In conclusion, Piper wallichii can be used as a candidate for the treatment of UC.

Changes in Nutritional Status of Cancer Patients Undergoing Proton Radiation Therapy Based on Real-World Data.

Methods: Observational study on 47 adult hospitalized cancer patients including 27 males and 20 females who received proton beam radiotherapy during December 2021 and August 2022. Nutritional assessments, 24 h dietary survey, handgrip strength (HGS) test, anthropometrical measurements, and hematological parameters were conducted or collected at the beginning and the completion of treatment. Results: The rate of nutritional risk and malnutrition among the total of 47 enrolled patients was 4.3% and 12.8% at the onset of proton radiation and raised up to 6.4% and 27.7% at the end of the treatment. 42.6% of patients experienced weight loss during the proton radiotherapy, and 1 of them had weight loss over 5%, and in general, the average body weight was stable over radiotherapy. The changes in patients' 24 h dietary intakes, HGS, and anthropometrical parameters, including triceps skinfold thickness (TSF), midupper arm circumference (MUAC), and midupper arm muscle circumference (MAMC), were statistically insignificant over the treatment (all p values > 0.05). The changes in patients' hematological parameters, including total protein (TP) and serum albumin (ALB), were not statistically significant over the treatment (all p values >0.05), and the level of hemoglobin (HGB) at the end of treatment was higher than that at the onset (p < 0.05). Conclusion: The results of this study demonstrated that proton radiotherapy might have a lighter effect on the nutritional status of cancer patients.

Exploring the mechanism of the Fructus Mume and Rhizoma Coptidis herb pair intervention in Ulcerative Colitis from the perspective of inflammation and immunity based on systemic pharmacology.

PURPOSE: Ulcerative Colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Fructus Mume (FM) and Rhizoma Coptidis (RC) exert effects on inflammatory and immune diseases. We evaluated the hypothesis of the FM and RC (FM-RC) herb pair remedy in alleviating dextran sulfate sodium (DSS)-induced colitis, through network pharmacology-based analyses, molecular docking, and experimental validation. METHODS: The Traditional Chinese medicine systematic pharmacology analysis platform(TCMSP) and Swiss database were used to predict potential targets of FM-RC and the GeneCards database was utilized to collect UC genes. Cytoscape software was used to construct and analyze the networks, and DAVID was utilized to perform enrichment analysis. AutoDock software was used to dock the core chemical components of the FM-RC herb pair with key UC targets. Animal experiments were performed to validate the prediction results and general conditions and body weight were observed. Pathological changes in colon tissue were observed by staining with hematoxylin and eosin. The levels of TNF-α, IL-8, IL-17, and IL-4 in serum and colon tissue were detected by ELISA. RESULTS: Eighteen effective components of the herb couple were screened, and their potential therapeutic targets in the treatment of UC were acquired from 110 overlapped targets. GO and KEGG analyses revealed that these targets were highly correlated with protein autophosphorylation, plasma membrane, ATP binding, cancer pathways, the PI3K-AKt signaling pathway, and the Rap1 signaling pathway. Molecular docking established the core protein interactions with compounds having a docking energy < 0 kJ·mol-1, indicating the core active components had strong binding activities with the core targets. FM-RC herb pair relieved pathological indicators and reduced the concentration of TNF-α, IL-8, and IL-17 and increased IL-4 levels in the serum and colon tissues of UC rats. CONCLUSION: Collectively, FM-RC herb pair administration alleviated UC. These beneficial effects targeted MAPK1 signaling related to inflammation and immunity, which provided a basis for a better understanding of FM-RC in the treatment of UC.

Rapid Characterization of Black Tea Taste Quality Using Miniature NIR Spectroscopy and Electronic Tongue Sensors.

The taste of tea is one of the key indicators in the evaluation of its quality and is a key factor in its grading and market pricing. To objectively and digitally evaluate the taste quality of tea leaves, miniature near-infrared (NIR) spectroscopy and electronic tongue (ET) sensors are considered effective sensor signals for the characterization of the taste quality of tea leaves. This study used micro-NIR spectroscopy and ET sensors in combination with data fusion strategies and chemometric tools for the taste quality assessment and prediction of multiple grades of black tea. Using NIR features and ET sensor signals as fused information, the data optimization based on grey wolf optimization, ant colony optimization (ACO), particle swarm optimization, and non-dominated sorting genetic algorithm II were employed as modeling features, combined with support vector machine (SVM), extreme learning machine and K-nearest neighbor algorithm to build the classification models. The results obtained showed that the ACO-SVM model had the highest classification accuracy with a discriminant rate of 93.56%. The overall results reveal that it is feasible to qualitatively distinguish black tea grades and categories by NIR spectroscopy and ET techniques.

Nephroprotective and nephrotoxic effects of Rhubarb and their molecular mechanisms.

Rhubarb, in the form of a traditional Chinese medicine, is used in the treatment of chronic kidney disease (CKD). Previous studies have demonstrated that Rhubarb possesses a good nephroprotective effect, which primarily protects the kidneys from fibrosis, oxidation, inflammation, autophagy, and apoptosis. However, studies have shown that the long-term inappropriate use of Rhubarb may cause damage to renal function. Therefore, how to correctly understand and scientifically evaluate the pharmacodynamics and toxicity of Rhubarb with regard to CKD is a scientific question that urgently needs to be answered. In this review, we explain and illustrate how Rhubarb exerts its nephroprotective effect against CKD. We also describe the mechanisms of action that may cause its nephrotoxicity. Valuable and practical clinical guidance is proposed with regard to methods for mitigating the nephrotoxicity of Rhubarb.

Eye Sign is an Alternative for Evaluation of the Microcirculation in Patients with Systemic Sclerosis.

Objectives: To investigate consistency between eye sign and nailfold video capillaroscopy (NVC) in systemic sclerosis (SSc) patients and to evaluate eye sign with various parameters of disease and potential pulmonary involvement. Methods: A total of 60 SSc patients and 20 healthy individuals were enrolled. 20 SSc patients were complicated with pulmonary arterial hypertension (PAH); 20 SSc patients with interstitial lung diseases (ILD); 20 SSc patients without pulmonary involvement. All subjects were assessed using the methods of NVC and eye sign. Skin involvement was evaluated by modified Rodnan skin score (mRSS) and disease activity according to Medsger's severity score (MSS). Clinical manifestations and the presence of autoantibodies were carefully recorded. Any correlations between were evaluated with the Spearman correlation coefficient test. Results: According to the morphological changes revealed by NVC, 3 types of NVC patterns have been characterized (early pattern, active pattern, and late pattern). Eye sign showed distinguishing morphologic changes in three patterns of NVC and pulmonary involvements (PAH vs ILD) in SSc. A positive linear correlation was found between scores of eye sign and NVC in all patients with SSc (r = 0.629, P=0.001). A positive correlation of eye sign was found in all SSc patients with mRSS (r = 0.748, P=0.045) and MSS (r = 0.636, P=0.001). Conclusions: The study demonstrates that eye sign had a high consistency with NVC for the evaluation of the microcirculation in SSc patients and exhibited specific patterns in the early, active, and late phases of SSc. Eye sign can be used as a reliable method to classify and monitor SSc patients and replace the measurement of NVC.