Background:Hemorrhoidal disease (HD) is characterized by the pathological dilation of anal vascular cushions, causing pain, itching and bleeding. Recent evidence links HD onset and progression to rectal inflammation. Medical Hemorrhoid Gel (MHG), a multi-component botanical preparation, has gained empirical validation for HD management. This study aims to systematically evaluate the safety, efficacy, and mechanism of action of MHG in treating HD. Methods:The phytochemical composition of MHG was characterized using UPLC-QTOF-MS/MS and GC-MS/MS analyses. In vivo, the efficacy was assessed in a croton oil preparation (COP)‑induced HD rat model (n=10 per group) via anorectal coefficient (ARC) measurement, macroscopic severity score, Evans blue extravasation quantification, and H&E/PAS staining. Transcriptomic sequencing of anorectal tissues was integrated with experimental validation using ELISA, immunohistochemistry (IHC), and Western blotting to delineate molecular mechanism. Data were analyzed by one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparison post hoc test (significance at p<0.05). Results:MHG significantly reduced ARC, macroscopic severity score, and Evans blue extravasation, restored intestinal villus structure and goblet cell numbers, and alleviated inflammation. Acute toxicity tests showed that MHG did not cause anorectal abnormalities or systemic toxicity in rats. Transcriptomic analysis integrated with experimental validation suggested the therapeutic mechanism of MHG involves inflammation response and NF-κB pathway. Specifically, MHG suppressed the levels of the pro-inflammatory mediator TNF-α, while it enhanced the levels of the anti-inflammatory mediator IL-10. Mechanistic studies revealed that MHG inhibited NLRP3 inflammasome activation, reduced the phosphorylation level of p65 and enhanced IκBα expression. Phytochemical analysis identified 20 constituents that contribute to the bioactivity of MHG. Conclusion:Our study substantiated that MHG exerts anti-hemorrhoidal effects through NLRP3 inflammasome suppression via NF-κB pathway regulation. This mechanistic insight provides scientific validation for clinical application of MHG in HD management.

BackgroundPruritus ani (PA), a neurofunctional dermatosis, is one of the most common complications of hemorrhoids, which seriously affects the quality of life of patients. Medical hemorrhoid gel (MHG), a product mainly composed of herbal medicine, is widely used for treatment of PA clinically. This study aim to assess the alleviating effect and mechanism of MHG on PA based on rectal epidermis-spinal cord-brain axis using animal models.MethodsA chloroquine-induced mouse itching model and a croton oil preparation-induced rat hemorrhoid model were established to evaluate anti-PA effect of MHG. Scratching behaviors of mice were recorded, and histopathology of mice skin and rat ano-rectal tissues was observed through H&E staining. Network pharmacology and western blotting were employed to explore potential mechanism of MHG.ResultsThe study indicated that MHG significantly alleviated chloroquine-induced skin itching and improved pathological injuries in mice skin and rat ano-rectal tissues. Network pharmacology suggested that MHG might regulate the JAK/STAT signaling pathway. Experimental findings showed that MHG significantly downregulated TRPV1 and TRPA1 in rectal tissue, c-Fos and GRPR in spinal cord tissue, and 5-HT1a protein in brain tissue, while upregulating TRPM8 protein in rectal tissue. Furthermore, MHG inhibited the activation of the JAK2/STAT3 signaling pathway in the rectal epidermis-spinal cord-brain axis.ConclusionMHG improves PA by inhibiting the transmission of itching signals in rectal epidermis-spinal cord-brain axis via the JAK2/STAT3 signaling pathway, providing experimental evidence for its clinical application.

Background. Angelica Yinzi (AYZ) is a Chinese traditional herbal formula reported to attenuate itches and inflammation caused by atopic dermatitis (AD). However, the underlying mechanism of AYZ in the attenuation of itchiness and inflammation remains unknown. Objective. This study investigated the mechanism of AYZ in reducing itchiness in mice with 1-chloro-2,4-dinitrobenzene- (DNCB-)-induced atopic dermatitis. Methods. Hematoxylin and eosin (H&E) and toluidine blue staining were used to evaluate pathological changes in skin tissue, while an enzyme‐linked immunosorbent assay (ELISA) was used to assess the cytokine levels in the skin. After that, qRT-PCR was performed to determine the mRNA levels of cytokines in the skin. Immunofluorescence and western blotting analysis were further used to assess µ-opioid receptor (MOR) expression and immunohistochemistry to assess the p-ERK, p-AKT, and κ-opioid receptor (KOR). Results. The AYZ treatment alleviated the AD clinical symptoms, including decreasing the scratching frequency, the ear thickness, and the infiltration of mast cells, lymphocytes, inflammatory cells, and mononuclear cells. In addition, AYZ inhibited the expression of interleukin (IL)-13, thymic stromal lymphopoietin (TSLP), and reduced neuraminidase (NA), corticotropin-releasing factor (CRF), and reactive oxygen species (ROS) expression. Markers involved in itches, such as p-ERK and p-AKT, were significantly downregulated following AYZ treatment. Besides, AYZ significantly increased MOR expression and downregulated KOR in the epidermis and spinal cord. Conclusion. Our findings imply that AYZ ameliorates pruritus-related AD through skin repair, antioxidation, and balancing peripheral MOR and KOR. The findings in this study lay a theoretical foundation for the control mechanism of peripheral itch.

Objective To evaluate the clinical effect of Mayinglong Zhichuang Gao（Gao, a TCM formula） in the treatment of hemorrhoids systematically. Methods Through CNKI and Wanfang databases searched all related literatures, the time ranges were from EST time of every databases to 2022-06-04,then, two literature researchers screened and evaluated the literatures, and by using RevMan5.4.1 software took Meta analysis on the enrolled literatures. Results After screening 11 pieces of Chinese literatures were included, then, took Meta analysis on the screened 11 pieces, totalled 2 125 cases of patients.Analysis showed compared to routine therapy for hemorrhoids Gao can lift clinical total effective rate, significantly relieve patients’ edema situation. Conclusion Gao’s efficacy are more great, can lift clinical effective rate, and provide more basis for TCM externally using to treat hemorrhoids.

Atopic dermatitis (AD), characterized by eczema as a chronic pruritic inflammatory skin disease, has become a serious health problem with recurrent clinical episodes. However, current clinical treatments have limited relief and are accompanied by adverse effects. Therefore, there is a necessity to develop new effective drugs for AD treatment. Angelica Yinzi (AYZ) is a classic ancient prescription for nourishing blood, moistening dryness, dispelling wind, and relieving itching. However, its mechanism for alleviating atopic dermatitis remains unknown. Therefore, this study aimed at determining the effects of AYZ and its potential mechanism in alleviating AD-like symptoms. In the present study, we used 1-chloro-2,4-dinitrobenzene (DNCB) to establish a mouse model of atopic dermatitis, where DNCB readily penetrates the epidermis to cause inflammation. Histopathological analysis was performed to examine the thickening of dorsal skin and infiltration in the inflammatory and mast cells in C57BL/6 mice. Additionally, the immunoglobulin E (IgE) levels in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The IL-1β and TNF-α expression were detected using qRT-PCR. Next, the Western blotting and immunohistochemistry assays were performed to assess the contribution of MAPKs/NF-κB signaling pathways and the NLRP3 inflammasome in AD responses. Histopathological examination revealed that AYZ reduced the epidermal thickness of AD-like lesioned skin and repressed the infiltration of mast cells into AD-like lesioned skin. AYZ significantly decreased the phosphorylation of p38 MAPK, JNK, ERK and NF-κB and downregulated serum IgE levels and IL-1β and TNF-α mRNA levels. Additionally, the NLRP3, ASC, Caspase-1, and IL-1β expression in dorsal skin were effectively down-regulated following AYZ treatment (p < 0.05 and p < 0.01). These findings revealed that AYZ effectively suppressed AD-induced skin inflammation by inhibiting the activation of the NLRP3 inflammasome and the MAPKs/NF-kB signaling. Therefore, AYZ is a potential therapeutic agent against AD in the clinical setting.

5,7-Dihydroxy-2-(1,2-isopropyldioxy-4-oxo-cyclohex-5-enyl)-chromen-4-one (DICO) is a novel non-aromatic B-ring flavonoid, isolated mainly from Macrothelypteris viridifrons and has anti-tumour properties. In this study, we investigated the cytotoxicity and underlying biochemical pathways leading to cell death, in response to DICO treatment of a human colon cancer cell line HT-29. Our results indicated that DICO induced apoptosis by elevating the generation of reactive oxygen species, which could be quenched by the antioxidants N-acetyl cysteine. In addition, activation of signal transducer and activator of transcription 3 and suppression of nuclear factor kappa B played a crucial role in DICO-induced apoptosis. Overall, our results provide mechanistic insights into the apoptotic action of a potential anti-tumour drug, DICO.

目的 观察八宝眼膏对暴露性角膜炎大鼠的治疗作用.方法 将32只大鼠随机分为4组,每组8只(8只眼):正常组、模型组、治疗组(八宝眼膏组)、阳性对照组(维生素A棕榈酸酯眼用凝胶组).将除正常组以外,其他组采用上下眼睑缝线固定法制造暴露性角膜炎模型,阳性对照组和治疗组分别于6d后给予维生素A棕榈酸酯眼用凝胶和八宝眼膏涂眼,每日2次.正常组和模型组不予处理.3d后,对各组大鼠进行眼表检查,检测泪液分泌量(SⅠt),荧光素钠染色(FL)、泪膜破裂时间(BUT)、组织病理学、Muc-5ac表达等.结果 (1)FL:正常组、阳性对照组和治疗组大鼠的FL为阴性.模型组大鼠FL为强阳性;(2)SⅠt:正常组与模型组相比,模型组大鼠的SⅠt显著降低(t=4.686,P=0.000).与模型组比较,阳性对照组、治疗组均显著增高(t阳性=4.246,t治疗=4.393;均P=0.001);(3)BUT:模型组BUT较正常组显著降低(t=-13.267,P=0.000),与模型组相比,阳性对照组和治疗组均显著增高(t阳性=12.507,t治疗=14.877;均P=0.000);(4)组织病理学:与模型组相比,治疗组、阳性对照组的角膜组织结构的完整性都有所改善,上皮层细胞排列较为紧密,实质层细胞的形态也较为规则;(5)Muc-5ac表达:与模型组相比,正常组、治疗组、阳性对照组Muc-5ac阳性着色部位均呈现较深颜色.结论 八宝眼膏对暴露性角膜炎引起的泪膜稳定性下降,角膜和结膜的损伤均有治疗作用.

A high-performance liquid chromatography method for the quantification of flavonoids from Macrothelypteris viridifrons (Tagawa) Ching, Thelypteridaceae, was developed. The analysis was performed on a C18 column with a gradient elution of methanol and water at a flow rate of 1 ml/min and a wavelength of 262 nm. All standard calibration curves exhibited good linearity (r2 > 0.9955) within the test ranges. The precision (intra-day and inter-day tests) revealed relative standard deviation values within the ranges of 0.54–2.03% and 0.84–2.38%, respectively. The recoveries were in the range of 97.51–100.19%. The relative standard deviation values for stability and repeatability were < 5%. The contents of protoapigenin-4′-O-glucoside and protoapigenone, as a class of unusual flavonoids, were high and varied in the range of 206.5–230.5 mg/g and 255.7–272.3 mg/g, respectively.

Objective:To observe laxative function of Shutong digestion powder in mice with constipation by experimental means to provide reference for clinical research. Methods:ICR mice were used as the research objects,and the mice model of constipation was induced by oral administration of loperamide hydrochloride. Totally 120 ICR mice were divided into two groups(experimental group 1 and experimental group 2) with 60 in each,and each group was divided into 6 subgroups by random number:the normal control group, the model control group,the positive control group(mosapride citrate tablets,2.25×10 -3g·kg-1),Shutong digestion powder group respectively at low(1 g·kg-1),medium(3 g·kg-1) and high dose(9 g·kg-1) with 10 ones in each. Drugs were given by intra-gastric administration,once a day,for 7 days. In the first experiment group,mice were subjected to defecation test,and the stool traits and the time of first defecation in each group were observed and recorded. In the experimental group 2,small intestine motility test was conducted to observe and record the ink advancing rate in intestine. Results:Compared with the model control group,there was no sig-nificant difference in the body weight of mice in each Shutong digestion powder group(P>0.05),and the time for the first row of me-lena significantly decreased(P<0.05 or P<0.01). The rate of small intestine propulsion increased except for Shutong digestion pow-der group at low dose,and the other groups had significant differences (P<0.05 or P<0.01). Compared with the positive control group,there was no significant difference in the body weight and the first defecation time between Shutong digestion powder groups and the control group (P>0.05). The ink advancing rates of Shutong digestion powder groups were lower than that of the positive control group (P<0.05 or P <0.01). Conclusion:Shutong digestion powder has good promotion function for defecation and intestinal peri-stalsis.

The present study aims to evaluate phytochemical and pharmacological potential of total protoflavones from Macrothelypteris viridifrons. In the phytochemical study, an HPLC analysis method was established, and the optimal extraction and purification conditions were analyzed. The extractive condition was optimized as follows: the backflow extraction with 20 folds of 70% ethanol at 80◦C for 1 h twice. Moreover, by combining the alkali-extraction and acid-precipitation method with the macroporous resin purification technology, the final purity rate of total protoflavones was no less than 54.85%. In the pharmacological study, the total protoflavones from M. viridifrons showed a significant tumor-inhibitory effect in the H22 hepatoma cells transplantation model with a higher inhibitory rate of 55.76% in high dosage (100mg/kg) treatment group compared with the positive control group (20 mg/kg cyclophosphamide). Taken of all, these results support that protoflavones are the material basis of M. viridifrons as an anticancer folk medicine.

Objective To research the chemical constituents from Parathelypteris glanduligera.Methods The compounds were isolated by column chromotography with silica gel,C18 reverse-phase silica gel,and Sephadex LH-20.Their structures were elucidated on the basis of physiochemical prosperities and spectral analysis.Results Eleven compounds were isolated and identified as kaempferol (1),astragaloside (2),trifolioside (3),kaempferol-3-O-α-L-rhamnopyranoside (4),kaempferol-3-O-rutinoside (5),quercetin (6),quercetin-3-O-β-D-galactopyranoside (7),rutin (8),myriciatrin I (9),3'-methyl-4',6'-dihydroxy-2'-methoxy-chalcone (10),and 3',5'-dimethyl-4',6'-dihydroxy-2'-methoxy-chalcone (11),respectively.Conclusion All compounds are obtained from this plant for the first time.

目的:研究柴术颗粒制剂提取工艺.方法:以浸膏固体物含量、柴胡皂苷、盐酸小檗碱、芍药苷提取量为指标进行正交试验,优选柴术颗粒提取工艺.结果:最佳提取工艺为炒白术、陈皮、干姜加5倍量水浸泡过夜,水蒸气蒸馏6h提取挥发油.白芍、茯苓等药材加入8倍量水,提取2次,每次1.5h,合并水提液,滤去药渣,备用;柴胡、黄连加入10倍量70％乙醇,提取2次,每次1.5h.结论:柴术颗粒处方药材根据其性质不同可分别采用水蒸气蒸馏法提取工艺、水提取工艺和乙醇提取工艺.

氯吡格雷是临床应用最广泛的抗血小板药物之一,但其临床疗效存在明显的个体差异,除临床因素外,遗传因素为另一个导致氯吡格雷疗效个体差异性的因素.氯吡格雷血小板高反应性(HTPR)相关基因的突变频率存在显著的种族差异,东亚人群的相关基因突变频率高于西方人群.目前研究表明,东亚人群发生氯吡格雷治疗期间HTPR的比例为20％～30％,高于西方人群,且CYP2C19*2和*3为HTPR的独立风险因素.通过增加氯吡格雷剂量,三联抗血小板治疗或换用新型P2Y12受体拮抗剂等策略可改善患者HTPR,并降低心血管事件的发生风险.

目的:研究复方蛇床子洗剂的制备工艺.方法:以蛇床子素、盐酸小檗碱含量为主要指标,对药材加水量、提取次数、提取时间等进行考察,从而优化提取工艺.结果:最佳提取工艺为:称取药材,加8倍水浸泡0.5h,加热提取3次,每次1.5h.趁热过滤,合并滤液,将滤液浓缩至相对密度约为1.1～1.2(60℃)的清膏,放冷至20～30℃,加入95％乙醇醇沉,使含醇量达80％,室温静置12～24h.醇沉液过滤,滤液减压浓缩至相对密度约为1.0～1.1(60℃),加水至适量,搅拌均匀即得.结论:该处方工艺制备的复方蛇床子洗剂适合于大生产工艺,质量稳定.

目的:系统评价甲巯咪唑和丙硫氧嘧啶治疗甲状腺功能亢进症的安全性.方法:检索中外文数据库,比较1994-2014年关于甲巯咪唑和丙硫氧嘧啶治疗甲亢出现粒细胞减少、肝损伤、皮疹主要不良反应的RCT,对结果进行Meta分析.结果:共纳入11个研究,涉及病例数1 660,Meta分析显示甲巯咪唑在治疗甲亢时引起粒细胞减少和皮疹的发生率与丙硫氧嘧啶无差别[RR=0.61,95％ CI (0.25,1.51),P=0.28;RR=0.88,95％ CI (0.66,1.17),P=0.38],但肝损伤的发生率比丙硫氧嘧啶低[RR=2.21,95％ CI (1.27,3.83),P=0.005].结论:甲巯咪唑治疗甲亢引起粒细胞减少和皮疹的风险与丙硫氧嘧啶相当,但肝损伤的风险比丙硫氧嘧啶低.

Objective:To analyze Jinxuan Zhike Xunxi powders ( JZX) and an active ingredients group ( AIG) obtained from JZX by GC-MS, and develop a characteristic fingerprint of AIG. Methods: A gas chromatography-mass spectrum ( GC-MS) method was applied to analyze the main compositions in JZX and AIG, and the characteristic fingerprint information in the fingerprint spectrum was determined. Results:Totally 10 batches of AIG were detected, and a promising GC-MS fingerprint spectrum containing characteristic information for AIG was obtained. Conclusion: The developed fingerprint with good repeatability can be successfully applied in the quality control of AIG.

ABSTRACT A simple and sensitive HPLC method using UV detection was developed to determine the concentration of protoapigenone in rat plasma. Chromatographic separation was conducted on a C 18 column with a mobile phase consisting of an acetonitrile–methanol–aqueous phase (containing 0.2% acetic acid, pH 3.0) system at a flow rate of 1.0 mL/min. The UV detector was set at 248 nm. The calibration curve was linear over the range of 0.031–10.0 µg/mL. The lower limit of quantification was 31 ng/mL. The recoveries for plasma samples ranged from 70.3 to 82.5%. The intra‐ and inter‐day accuracy and precision fulfilled the international standards. This method was successfully applied to a pharmacokinetic study of protoapigenone in rats after oral administration of protoapigenone. It was shown that protoapigenone could be absorbed rapidly after oral administration and could reach the maximum concentration within 1 h. Copyright © 2013 John Wiley & Sons, Ltd.

DICO was a novel nonaromatic B-ring flavonoid obtained from Macrothelypteris torresiana. In the present work, we investigated the antitumor activity and the antineoplastic mechanism of DICO. Our study showed that DICO inhibited the growth of HepG2 cells in dose and time-dependent manners. As well as DICO induced G2/M cell cycle arrest and apoptosis via a ROS-mediated mitochondrial pathway. Western blot assay demonstrated that DICO decreased Bcl-2 level and induced Bax translocation to cause cytochrome c release. Subsequently, caspase-9 and caspase-3 were activated. Meanwhile, the alterations of cyclin A and B1, p-CDK1 and p-cdc25c levels were also observed in response to DICO treatment. Taken together, DICO displayed a significant antitumor effect through G2/M cell cycle arrest and apoptosis induction, which suggested DICO might have therapeutic potential against tumors.

Ethnopharmacological relevance: Macrothelypteris viridifrons is widely distributed in south of China and has been used as folk medicine to treat cancer, hydropsy, and traumatic bleeding.Aim of the study: To investigate the chemical constituents and the anti-tumor and anti-angiogenic effects of Macrothelypteris viridifrons.Materials and methods: An HPLC-DAD/MS technique was used to determine the flavonoid profile of Macrothelypteris viridifrons. The anti-tumor effect of Macrothelypteris viridifrons was evaluated by in vivo mice bearing H22 hepatoma cells transplantation tumor model. And the anti-angiogenic activity was investigated by measuring the effects on the in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo zebrafish model was applied to evaluate the anti-angiogenic effect of Macrothelypteris viridifrons.Results: 18 flavonoids were identified from Macrothelypteris viridifrons. Administration of Macrothelypteris viridifrons significantly inhibited the tumor growth and the expression of vascular endothelial growth factor (VEGF) and CD34. Meanwhile, Macrothelypteris viridifrons showed significant inhibition on proliferation, migration and tube formation of HUVECs in vitro and the intersegmental vessels formation in zebrafish model.Conclusions: Macrothelypteris viridifrons showed significant anti-tumor and anti-angiogenic effects and might be developed as a novel anti-tumor drug. (C) 2011 Elsevier Ireland Ltd. All rights reserved.