An effective treatment for diabetic foot necrosis with traditional Chinese and Western medicine: a case report.

Patients with diabetes who undergo a kidney transplant are at a great risk of undergoing amputations, usually associated with severe infection and necrosis. The treatment of severe diabetic foot necrosis is challenging in clinic, and the function of the limb is often hugely compromised. A 74-year-old male who had been diagnosed with severe post-renal transplant diabetic foot necrosis refused the option of below-knee amputation from previous surgeons, and requested to keep his left foot. The patient was treated with integrated traditional Chinese medicine (TCM) and Western medicine, with positive results. TCM therapeutic principles included 'clearing heat, removing toxicity, regulating Qi, resolving dampness, activating stagnant blood and nourishing yin as well as tonifying Qi and blood'. Treatment with Western medicine included wound debridement, internal fixation or joint fusion, and use of insulin, antibiotics and vasodilators. The patient was treated with a staged and diverse approach (i.e., a combination of TCM and Western medicine, surgical management and education for diabetic foot care), which ultimately helped the patient achieve limb salvage and regain normal function. A combination therapy of Western medicine and TCM may be a promising approach to heal diabetic foot ulcers.

Ruan Jian Qing Mai's Formula Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration and Proliferation.

Objective: To investigate the response of (BM-MSCs) to the Ruan Jian Qing Mai formula (RJQM) in the treatment of atherosclerotic occlusion (ASO), and consequently promoting the development of collateral circulation and angiogenesis. Method: 35 male rats were randomly assigned to 6 experimental groups and A control group. 0.9% NaCl solution and 2.7, 5.4, 10.8, 16.2, 21.6, and 27 g × kg-1 × d-1 of RJQM formula were gavaged to the experimental groups twice a day for 8 days. After the last administration, medicated serum was prepared from the blood collected from the abdominal aorta. The human BM-MSCs were divided into an experimental group and a control group. A blank group of cells was added with a complete medium without rat serum; an experimental group of cells was added with the prepared drug-containing serum. Under hypoxic conditions, the drug-containing serum was used to treat BM-MSCs and/or endothelial cells of human umbilical vein (HUVECs). A Cell counting kit (CCK8) was used to detect cell proliferation. Western blot (WB) and quantitative real-time PCR (qPCR) were used to identify related genes expression. Results: The results of this study showed that the purity of the BM-MSCs was >95%. The drug-containing serum significantly rise in CCND1 expression (encoding cyclin D1) and MYC, especially when the concentration of medicated serum was 10.8 g × kg-1 × d-1. Treatment of either BM-MSCs or HUVECs alone or both with medicated serum aids in the spread of mesenchymal stem cells from the bone marrow to HUVECs. qPCR results showed that the mRNA expression of CCL2, CCL3, CCL25, IL8, IGF1, and PDGFB increased dramatically after treatment with medicated serum. The expression of the corresponding receptors for these up-regulated chemokines was detected in BM-MSCs, and it was found that CXCR1, CXCR4, CXCR7, and PDGFRB were up-regulated. Conclusion: This study provides a preliminary understanding of the mechanism of RJQM in the treatment of ASO.

Characterization of walnut protein isolate-polyphenol nanoconjugates for the developing a food-grade delivery system.

This study investigated the effects of the interaction of walnut protein isolate (WPI) with epigallocatechin gallate (EGCG), chlorogenic acid (CLA), (+)-catechin (CA), and ellagic acid (EA) on the structural and functional properties of proteins. The results for polyphenol binding equivalents and content of free amino and sulfhydryl groups as well as those from sodium dodecyl sulfate‒polyacrylamide gel electrophoresis confirmed the covalent interaction between WPI and the polyphenols. The binding capacities of the WPI-polyphenol mixtures and conjugates were as follows: WPI-EGCG > WPI-CLA > WPI-CA > WPI-EA. Fourier transform infrared spectroscopy (FTIR) and fluorescence spectrum analysis identified changes in the protein structure. The conjugation process obviously increased the polyphenols' antioxidant properties and the surface hydrophobicity was substantially reduced. WPI-EGCG conjugates had the best functional properties, followed by WPI-CLA, WPI-CA, and WPI-EA. Lycopene (LYC) was loaded into nanocarriers by WPI-EGCG self-assembly. These results indicated that WPI-polyphenol conjugates can be utilized to develop food-grade delivery systems to protect chemically lipophilic bioactive compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05768-2.

In-Tumor Biosynthetic Construction of Upconversion Nanomachines for Precise Near-Infrared Phototherapy.

Targeted construction of therapeutic nanoplatforms in tumor cells with specific activation remains appealing but challenging. Here, we design a cancer-motivated upconversion nanomachine (UCNM) based on porous upconversion nanoparticles (p-UCNPs) for precise phototherapy. The nanosystem is equipped with a telomerase substrate (TS) primer and simultaneously encapsulates 5-aminolevulinic acid (5-ALA) and d-arginine (d-Arg). After coating with hyaluronic acid (HA), it can readily get into tumor cells, where 5-ALA induces efficient accumulation of protoporphyrin IX (PpIX) via the inherent biosynthetic pathway, and the overexpressed telomerase prolonged the TS to form G-quadruplexes (G4) for binding the resulting PpIX as a nanomachine. This nanomachine can respond to near-infrared (NIR) light and promote the active singlet oxygen (1O2) production due to the efficiency of Förster resonance energy transfer (FRET) between p-UCNPs and PpIX. Intriguingly, such oxidative stress can oxidize d-Arg into nitric oxide (NO), which relieves the tumor hypoxia and in turn improves the phototherapy effect. This in situ assembly approach significantly enhances targeting in cancer therapy and might be of considerable clinical value.

Treatment strategies and pharmacist-led medication management for Helicobacter pylori infection.

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.

Exploring the potential mechanism of Simiao Yongan decoction in the treatment of diabetic peripheral vascular disease based on network pharmacology and molecular docking technology.

The study aims to investigate the potential action targets and molecular mechanisms of Simiao Yongan decoction (SMYAD) in treating diabetic peripheral vascular disease (DPVD) by utilizing network pharmacology analysis and molecular docking technology. The components and targets of SMYAD were screened using the TCMSP database, while DPVD-related genes were obtained from the GeneCards, OMIM, and Disgenet databases. After intersecting the gene sets, a Protein-Protein Interaction (PPI) network was established, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. The practical chemical components and core targets identified were molecularly docked using AutoDock software. A total of 126 active compounds were screened from which 25 main components included quercetin, rutoside, hesperidin, naringin, and ß-sitosterol were determined to be the active components most associated with the core targets. A total of 224 common target genes were obtained. Among them, JUN, AKT1, MAPK3, TP53, STAT3, RELA, MAPK1, FOS, and others are the expected core targets of traditional Chinese medicine. The top-ranked GO enrichment analysis results included 727 biological processes (BP), 153 molecular functions (MF), and 102 cellular components (CC). KEGG pathway enrichment analysis involved mainly 178 signaling pathways, such as cancer signaling pathway, AGE-RAGE signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, endocrine resistance signaling pathway, cell aging signaling pathway, and so on. The molecular docking results demonstrate that the principal chemical components of SMYAD exhibit considerable potential for binding to the core targets. SMYAD has the potential to treat DPVD through various components, targets, and pathways. Its mechanism of action requires further experimental investigation.

Multimodal integrated strategy for the discovery and identification of quality markers in traditional Chinese medicine.

With the modernization and internationalization of traditional Chinese medicine (TCM), the requirement for quality control has increased. The quality marker (Q-marker) is an important standard in this field and has been implemented with remarkable success in recent years. However, the establishment of Q-markers remains fragmented and the process lacks systematicity, resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM. This review introduces four multimodal integrated approaches that contribute to the discovery of more comprehensive and accurate Q-markers, thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM. These include the whole-process quality control strategy, chemical-activity-based screening method, efficacy, safety, and consistent combination strategy, and TCM theory-guided approach. Furthermore, methodologies and representative examples of these strategies are described, and important future directions and questions in this field are also proposed.

Ruan Jian Qing Mai Recipe Inhibits the Inflammatory Response in Acute Lower Limb Ischemic Mice through the JAK2/STAT3 Pathway.

Ruan jian qing mai recipe (RJQM) is an empirical prescription for treating arteriosclerosis obliterans (ASO). However, the mechanism of RJQM recipe-mediated ASO attenuation has not yet been elucidated. Therefore, this study aimed to explore the mechanism by which the RJQM recipe relieves ASO in a mouse model of lower limb ischemia, which was established by ligating and breaking the femoral artery of the left lower limb. The surgical groups were divided into the ischemic group, beraprost sodium group, low-dose RJQM group, medium-dose RJQM group, and high-dose RJQM group. Normal mice were set as the control group. The blood flow of the lower limb was examined on days 7 and 14. At the end of animal procedures, blood samples were collected, and the rectus femoris of the left lower limb were harvested. Results revealed that mice in the ischemic group demonstrated low blood flow. Additionally, hematoxylin and eosin, and Masson staining results showed that inflammation of the rectus femoris was obvious in the ischemia group, and the level of fibrosis was increased. Blood flow was recovered in all treatment groups compared to the ischemic group, and the inflammatory infiltration and fibrosis of the rectus femoris were relieved after RJQM treatment. The serum levels of interleukin (IL)-17A and IL-21 were decreased, and the expression of JAK2/STAT3 proteins was inhibited in all RJQM treatment groups compared to the ischemia group. Furthermore, the improvement of IL-17A, IL-21, and rectus femoris fibrosis was more obvious with increasing treatment time. In conclusion, RJQM can effectively alleviate ASO and promote the recovery of lower limb blood flow by regulating the JAK2/STAT3 signaling pathway to reduce the inflammatory response.

The in vitro and in vivo antibacterial activities of uniflorous honey from a medicinal plant, Scrophularia ningpoensis Hemsl., and characterization of its chemical profile with UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Compendium of Materia Medica, honey has been used as a traditional medicine in treatment against mucositis, tinea, hemorrhoids and psoriasis. In complementary medicine, due to its significant antimicrobial activity, honey has been widely used as a remedy for skin wounds and gastrohelcosis for thousands of years. AIM OF THE STUDY: This study is aimed at exploring the antimicrobial activity and mechanisms of honey sourced from medicinal plants, and revealing the composition-activity relationship, to facilitate their complementary and alternative application in the therapy of bacterial infectious diseases. MATERIALS AND METHODS: Eight kinds of medicinal plant-derived uniflorous honey, native to China, were gathered. Their antimicrobial activities were evaluated in vitro, and then in vivo with the systemically infected mouse model and the acute skin infection model. SYTOX uptake assay, scanning electron microscopy, DNA binding assay, and quantitative real-time PCR, were carried out to elucidate the antibacterial mechanisms. This was followed by an investigation of the componential profile with the UPLC-MS/MS technique. RESULTS: It was found that Scrophularia ningpoensis Hemsl. (figwort) honey (S. ningpoensis honey) exhibited broad-spectrum and the strongest antibacterial potency (MICs of 7.81-125.00%, w/v), comparable to manuka honey. In the in vivo assays, S. ningpoensis honey significantly decreased the bacterial load of the muscles under the acute MRSA-infected skin wounds; the sera level of TNF-α in the S. aureus and P. aeruginosa-infected mice decreased by 45.38% and 51.75%, respectively, after the treatment of S. ningpoensis honey (125 mg/10 g). It was capable of killing bacteria through disrupting the cell membranes and the genomic DNA, as well as down-regulating the expression of genes associated with virulence, biofilm formation and invasion, including icaA, icaD, eno, sarA, agrA, sigB, fib and ebps in S. aureus, and lasI, lasR, rhlI, rhlR and algC in P. aeruginosa. Apart from H2O2, some other nonperoxide compounds such as adenosine, chavicol, 4-methylcatechol, trehalose, palmitoleic acid and salidroside, might play a vital role in the antibacterial properties of S. ningpoensis honey. CONCLUSIONS: This is the first study to thoroughly investigate the antibacterial activity, mode of action, and componential profile of S. ningpoensis honey. It suggested that S. ningpoensis honey might be a potential supplement or substitute for manuka honey, for the prevention or treatment of bacterial infections. It will facilitate the precise application of medicinal plant-sourced honey, provide a new thread for the development of antibacterial drugs, and assist in the distinction of different kinds of honey.

An integrated network pharmacology and cell metabolomics approach to reveal the role of rhein, a novel PPARα agonist, against renal fibrosis by activating the PPARα-CPT1A axis.

BACKGROUND: Rhein, an anthraquinone compound, displays extensive antifibrotic effects; however, its potential mechanisms are not fully understood. In this study, we explored the underlying molecular mechanism of action of rhein. METHOD: An integrated network pharmacology and cell metabolomics approach was developed based on network pharmacology and bioinformatics method, and then successfully applied to speculate the potential targets of rhein and construct a rhein-target-metabolic enzyme-metabolite network. Thereafter, the antifibrotic mechanism of rhein was validated in TGF-ß- and oleic acid- induced HK-2 and NRK-52E cells in vitro as well as a unilateral ischemia-reperfusion injury Sprague-Dawley rat model. RESULTS: Based on the construction of the rhein-target-metabolic enzyme-metabolite network, we found that rhein played an antifibrotic role through the PPAR-α-CPT1A-l-palmitoyl-carnitine axis. In vitro experiments demonstrated that rhein effectively activated the expression of PPARα and its downstream proteins (CPT1A and ACOX1) to alleviate lipid accumulation and fibrosis development. In vivo experiments indicated that rhein attenuated renal fibrosis mainly by activating the fatty acid oxidation pathway and improving lipid metabolism. CONCLUSION: Taken together, our findings reveal that rhein is a novel agonist of PPARα, which contributes to its renoprotection through the regulation of the PPARα-CPT1A axis. Moreover, our study provides a novel insight into an integrated network pharmacology-metabolomics strategy for uncovering the pharmacological mechanisms of drugs from the system perspective.

The chemical and metabolite profiles of Gualou-Xiebai-Banxia decoction, a classical traditional Chinese medicine formula, by using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and in-house software.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou-Xiebai-Banxia decoction (GXBD) was a classical traditional Chinese medicine formula for the treatment of coronary heart disease. However, the current study on the chemical and metabolite profiles of GXBD did not follow the ancient prescription and extraction method, which hindered the discovery of effective compounds and quality control. MATERIALS AND METHODS: In this study, we prepared GXBD by ancient prescription and extraction methods, and then analysed the chemical components and xenobiotics of GXBD in vivo using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and in-house software. RESULTS: 49 chemical constituents were preliminarily identified, including 7 terpenoids, 6 flavonoids, 5 alkaloids, 17 organic acids, 8 steroids and steroidal saponins, 2 nucleosides and 4 other types of compounds, of which 10 constituents were confirmed unambiguously with authentic standards. Moreover, 129 metabolites were tentatively identified, including 83 metabolites in plasma, 39 metabolites in urine, 25 metabolites in bile and 9 metabolites in feces. Our study speculated that luteolin, adenosine, vanillic acid and curbitacin B might be possible effective components of GXBD for the treatment of coronary heart disease. Dehydration, deglycosylation, dehydrogenation, acetylation and taurine regulation were the main biotransformation reactions of GXBD. CONCLUSION: Our results provided an important basis for the discovery of effective compounds and quality control of GXBD. In addition, in-house software was an useful tool for identifcation of metabolites.

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis.

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1ß, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

[Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice].

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Strength and size of phosphorus-rich patches determine the foraging strategy of Neyraudia reynaudiana.

BACKGROUND: Under natural conditions, soil nutrients are heterogeneously distributed, and plants have developed adaptation strategies to efficiently forage patchily distributed nutrient. Most previous studies examined either patch strength or patch size separately and focused mainly on root morphological plasticity (increased root proliferation in nutrient-rich patch), thus the effects of both patch strength and size on morphological and physiological plasticity are not well understood. In this study, we examined the foraging strategy of Neyraudia reynaudiana (Kunth) Keng ex Hithc, a pioneer grass colonizing degraded sites, with respect to patch strength and size in heterogeneously distributed phosphorus (P), and how foraging patchily distributed P affects total plant biomass production. Plants were grown in sand-culture pots divided into ½, », 1/6 compartments and full size and supplied with 0 + 0/30, 0 + 7.5/30 and 7.5 + 0/30 mg P/kg dry soil as KH2PO4 or 0 + 15/15, 0 + 18.5/ 18.5, 7.5 + 15/15 mg kg - 1 in the homogenous treatment. The first amount was the P concentration in the central region, and that the second amount was the P concentration in the outer parts of the pot. RESULTS: After 3 months of growth under experimental conditions, significantly (p < 0.05) high root elongation, root surface area, root volume and average root diameter was observed in large patches with high patch strength. Roots absorbed significantly more P in P-replete than P-deficient patches. Whole plant biomass production was significantly higher in larger patches with high patch strength than small patches and homogeneous P distribution. CONCLUSION: The result demonstrates that root morphological and physiological plasticity are important adaptive strategies for foraging patchily distributed P and the former is largely determined by patch strength and size. The results also establish that foraging patchily distributed P resulted in increased total plant biomass production compared to homogeneous P distribution.

A comparative study on the clinical effect of the treatment of pathological scars in young and middle-aged women with the combination of Chinese and western medicine.

INTRODUCTION: Pathological scar is the abnormal manifestation of skin fiber hyperplasia caused by the failure of normal healing after skin damage. At present, there are many clinical treatments for pathological scars. However, there is no cure for clinically effective pathological scars with high recurrence rate. In this study, we will use a combination of Chinese and western medicine treatment methods to evaluate the clinical efficacy and related indicators of young and middle-aged female patients who meet pathological scars, looking for an objective and effective treatment method for pathological scars. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for pathological scars. The untreated pathological scars of the enrolled patients will be used as blank controls. The intervention group will be given conventional western medicine treatment and combined Chinese and western medicine treatment. The assessment of scar area, color, hardness, thickness, itching, and pain was recorded for 8 weeks of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of traditional Chinese medicine for patients with pathological scars. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032187, Registered on April 22, 2020.

Clinical observation for acupuncture treatment of a small area of hyperplastic scars in young and middle-aged women.

INTRODUCTION: Hypertrophic scars are a common disease in plastic surgery, which is the reaction of skin connective tissue to trauma beyond the normal range. Although scholars around the world have explored the tissue structure and formation mechanism of HS for decades, they are not satisfactory the result of. No effective treatment has been found. Therefore, the search for safe and effective treatments for HS has always been the focus of medical attention and research. Acupuncture therapy has a definite effect on HS and has unique advantages. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for HS. The untreated HS of the enrolled patients will be used as blank controls. The intervention group will be given acupuncture treatment. The assessment of scar area, color, hardness, thickness, itching and pain will be recorded for 30 days of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Acupuncture for patients with HS. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032624, Registered on 04 May 2020.

In vitro effects of peimine on the activity of cytochrome P450 enzymes.

Peimine is a major component of Fritillaria ussuriensis, which is a widely used herb in pediatric. It is very common in Chinese traditional medicine to combine with two or more herbs in the clinic. To investigate the effect of peimine on the activity of cytochrome P450 enzymes (CYP450) is necessary for the clinical application of peimine.The effects of peimine on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro in human liver microsomes (HLMs) with the specific inhibitors as positive control and without peimine or inhibitors as negative control. The enzyme kinetic parameters were calculated.It was found that peimine inhibited the activity of CYP3A4, 2E1, and 2D6 in a concentration-dependent manner with the IC50 values of 13.43, 21.93, and 22.46 µM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the Ki value of 6.49 µM, and the inhibition of CYP2E1 and 2D6 was performed in a competitive manner with Ki values of 10.76 and 11.95 µM. Additionally, peimine inhibited the activity of CYP3A4 in a time-dependent manner with the KI/Kinact value of 6.17/0.049 min-1 µM-1.Peimine inhibited the activity of CYP3A4, 2E1, and 2D6, which indicated the potential interaction between peimine and drugs metabolized by CYP3A4, 2E1, and 2D6. Further studies are needed to verify the drug-drug interaction and the in vivo effects.

Ultrasound-Assisted Preparation of Exopolysaccharide/Nystatin Nanoemulsion for Treatment of Vulvovaginal Candidiasis.

PURPOSE: As one of the classic anti-Canidia albicans (CA) and vulvovaginal candidiasis (VVC) drugs, nystatin (NYS) is limited by poor water solubility and easy aggregation. Traditional NYS vaginal delivery formulations do not fully adapt to the specific environment of the vaginal cavity. The use of exopolysaccharides (EPS) has great application potential in emulsifiers, but its use has not been reported in nanoemulsions. In this work, an EPS/NYS nanoemulsion (ENNE) was developed to improve the activities of NYS against CA and VVC. METHODS: The ENNE was prepared by ultrasonic method using EPS as an emulsifier, liquid paraffin oil as an oil phase, PEG400 as a co-emulsifier, and NYS as the loaded drug. ENNE preparation was optimized by response surface method. After optimization, in vitro and in vivo analysis of the anti-CA activity; animal experiments; staining with propidium iodide (PI), periodic acid-schiff (PAS), and hematoxylin-eosin (H&E); and cytokine experiments were performed to investigate the therapeutic ability against VVC. RESULTS: The optimal formulation and preparation parameters of ENNE were determined as follows: EPS content of 1.5%, PEG400 content of 3.2%, NYS content of 700 µg/mL, paraffin oil content of 5.0%, ultrasonic time of 15 min, and ultrasonic amplitude of 35%. The ENNE showed an encapsulated structure with an average particle size of 131.1 ± 4.32 nm. ENNE exhibited high storage and pH stability, as well as slow release. The minimum inhibitory concentration (MIC) of ENNE against CA was only 0.125 µg/mL and the inhibition zone was 19.0 ± 0.5 mm, for greatly improved anti-CA effect. The prepared ENNE destroyed the membrane of CA cells, and exhibited good anti-CA effect in vivo and therapeutic ability against VVC. CONCLUSION: The results of this study will promote the application of EPS in nanotechnology, which should lead to new and effective local drug formulations for treating VVC.

Integrating serum exosomal microRNA and liver microRNA profiles disclose the function role of autophagy and mechanisms of Fructus Meliae Toosendan-induced hepatotoxicity in mice.

Herb-induced liver injury (HILI) is a growing clinical and economic problem worldwide. However, the underlying mechanism of HILI remains largely unknown, which hinders the prevention and treatment of this disease. Recently evidence supports that microRNAs (miRNAs) in circulating exosomes and cells play an important role in the pathology of liver diseases. Thus, using Fructus Meliae Toosendan (FMT) as an example of hepatoxic herbal medicine, the aim of this study was to reveal the mechanisms of FMT-induced liver injury (FILI) through integrated analysis of serum exosomal miRNAs and liver miRNAs profiles on FMT ethyl acetate extract (FMT for short)-exposed mice. Two dosages of FMT (20 and 40 g/kg) were involved in this study, while only high-dose exposure induced obvious liver injury in mice. Pathway analysis of 209 differentially expressed miRNAs (DEMs) in serum exosomes between high-dose FMT and control groups exhibited that FILI might be regulated by apoptosis-related pathways, such as p53 signaling, PI3K/Akt signaling, and PTEN signaling. Integrated analysis of the mRNA targets of serum exosomal DEMs and liver DEMs of high-dose FMT group showed that autophagy was significantly enriched as one of the top canonical pathways in FILI. Hepatocyte apoptosis was then proved by TUNEL assay in the liver tissue of high-dose FMT-treated mice. Moreover, in vivo validation studies suggested that the protein expression levels of PTEN, p-AKT, p53, and BAX were indeed regulated in the mouse liver after high-dose FMT administration, indicating hepatocyte apoptosis may be mediated by these three pathways mentioned above. Intriguingly, PINK1/Parkin-mediated mitophagy was activated in high-dose FMT-treated mouse liver and the protective effect of autophagy in FILI was validated in vitro with an autophagic flux inhibitor. In addition, serum exosomal miR-222, the most downregulated miRNAs between low- and high-dose FMT treatments, might be an important event in the hepatocyte apoptosis by regulating PTEN and PPP2R2A. In conclusion, integrated analysis of microRNA profiles in mouse serum exosomes and liver cells provides insights into the hepatotoxicity mechanisms of FMT and discloses the protective role of autophagy in FILI, suggesting this method could contribute to deeply understand the mechanism of HILI and activation of autophagy may be a potentially therapeutic strategy for FILI even HILI.

Corn silk extract inhibit the formation of Nε-carboxymethyllysine by scavenging glyoxal/methyl glyoxal in a casein glucose-fatty acid model system.

Herein, corn silk extract and its flavonoids were used to inhibit the formation of Nε-carboxymethyllysine (CML) in a casein glucose-fatty acid model system. Under these optimum extraction conditions, nine major flavonoids were identified and quantified by HPLC-MS/MS. The percent inhibition of CML formation by corn silk extract was 76.57%. The inhibitory mechanism of corn silk extract toward CML formation was further investigated by examining the trapping of glyoxal/methyl glyoxal by the major flavonoids (5 mM) using HPLC-ESI-MS, and mono-, di-, and tri-adducts were found for some flavonoid compounds. The antioxidant activity of the corn silk extract was evaluated by the DPPH and ABTS assays. The scavenging activity of the corn silk extract for DPPH and ABTS was 84.38% and 89.11%, respectively. The results suggested that corn silk extract inhibited CML formation through glyoxal/methyl glyoxal scavenging or by its antioxidant activity attributed to its flavonoid content.