Promise of the gut microbiota in prevention and traditional Chinese medicine treatment of diabetic peripheral neuropathy

The pathogenesis of diabetic peripheral neuropathy(DPN)has not been fully elucidated,and treatment options are limited.Currently,the main strategies for treating DPN are strict glycemic control and symptomatic pain relief.In this editorial,we comment on an article by Li et al,which suggested that modulating the gut microbiota using traditional Chinese medicine(TCM)may be a promising strategy for alleviating DPN symptoms.The regulation of the gut microbiota has received widespread attention in the study of various diseases.TCM can parti-cipate in the regulation of gut microbiota through multiple mechanisms,and this regulatory effect can alleviate the clinical symptoms of DPN.We briefly analyzed the promise of the gut microbiota in the early diagnosis,treatment,and clinical efficacy of TCM for DPN.The gut microbiota has potential value at multiple no-des in the occurrence and progression of DPN.

Mechanisms of liver injuries caused by traditional Chinese medicines

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

Potential prospects of Chinese medicine application in diabetic retinopathy

Current treatment strategies for diabetic retinopathy(DR),an eye condition that can lead to blindness,have mainly focused on proliferative DR,including vitreous injection,retinal photocoagulation,and vitrectomy.Vitreous injections mainly depend on anti-vascular endothelial growth factor therapy.In this editorial,we comment on the article by Sun et al.We focus specifically on the mechanisms of the protective effect of genipin on the retina.Genipin is a gardenia extract used in traditional Chinese medicine(TCM).In their study,the authors suggest that controlling advanced glycosylation by the intraocular injection of genipin may be a strategy for preventing retinopathy.The innovative use of a Chinese medicine extract injected into the eye to achieve a curative effect has attracted our attention.Although TCM is effective in treating DR,the topical application of DR,especially intraocular injections,is not yet feasible.Herein,we present a brief analysis of effective Chinese medicines for the treatment of DR.The effectiveness of local injections of TCM applied directly into the eyes holds promise as an effective treatment approach for DR.

Insight into the efficacy and safety of pirfenidone: The treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)has a poor prognosis if left untreated;therefore,early treatment with pirfenidone is crucial.Lei et al conducted a retrospective analysis to evaluate the effectiveness of early pirfenidone treatment on lung function in 113 patients with IPF.In addition to other research,pirfeni-done has demonstrated efficacy in patients at all stages of IPF once correct diagnosis has been made.In advanced IPF,we include the requirement for pirfenidone.Therefore,it is essential to choose an appropriate method of adminis-tration method,such as inhalation.This may circumvent the drawbacks of the high cost and possible adverse effects of this drug.

Identifying medication regularity of traditional Chinese medicine and potential pharmacological mechanism of Jiedu Sangen decoction in colorectal cancer treatment by data mining and network pharmacology

Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment remain unclear.Therefore,data mining combined with network pharmacology was utilized to establish treatment principles and rules.Methods:The CRC cases treated at Zhejiang Provincial Hospital of Chinese Medicine from January 1,2016 to October 31,2021 were analyzed using data mining methods.UPLC-Q/TOF-MS analysis was performed to identify the chemical composition of Jiedu Sangen decoction(JSD).Network pharmacology was used to reveal the therapeutic mechanism of JSD.Results:A total of 312 cases 2,998 prescriptions that met the inclusion criteria used 343 kinds of traditional Chinese medicines.The nature of the herbs used in treatment was mainly warm and mild.The taste was mainly sweet,bitter,and pungent.The meridian tropisms were mainly the spleen meridian,followed by lung and stomach meridians.Tonifying and replenishing herbs were the most frequently used in treatment.High-frequency herbs were classified into 11 categories by cluster analysis,and 42 association rules were obtained by association rule analysis.Combined with complex network analysis,3 core prescriptions for clinical CRC treatment were obtained.Jiedu Sangen decoction contains 64 chemical ingredients,out of which 31 active ingredients were identified,including polydatin,caffeic acid,and glutamic acid,along with 130 potential targets such as AKT1,SRC,and MAPK1.Jiedu Sangen decoction may play a role in regulating inflammation,immunity,metabolism,and hormones in the development of CRC via pathways such as the relaxin signaling pathway,IL-17 signaling pathway,prolactin signaling pathway,and T cell receptor signaling pathway.Conclusions:This study summarizes the treatment and medication principles for clinical CRC treatment,promoting the inheritance and development of the traditional Chinese medical experience.

Integrated Medicine Treatment of Rare Bone Marrow Tuberculosis in Systemic Lupus Erythematosus and Potentiating and Detoxifying Effects of Chinese Medicine:A Case Report

Systemic lupus erythematosus(SLE)is an autoimmune disease that affects multiple organ systems.(1,2)Patients with SLE who undergo long-term immunosuppressive and glucocorticoids therapy are at an elevated risk of developing tuberculosis(TB).

Implementation of gastrointestinal function protection in severe acute pancreatitis

Severe acute pancreatitis(SAP)is a serious systemic disease associated with strong local inflammatory reactions and serious systemic pathophysiological disorders caused by trypsin spillover.Patients with SAP are prone to exhibit gastrointestinal dysfunction.Meanwhile,gastrointestinal dysfunction further aggravates the systemic inflammatory response and metabolic abnormalities,resulting in a more critical condition of SAP.Gastrointestinal dysfunction is considered to be the“trigger”of multiple organ dysfunction syndrome[1].Thus,it is important to maintain gastrointestinal homeostasis in the treatment of SAP.

New strategy for distal limb perfusion in veno-arterial extracorporeal membrane oxygenation treatment: application of continuous renal replacement therapy tubing

Extracorporeal membrane oxygenation(ECMO)is a technology that can temporarily take over the functions of the heart and lungs.Acute kidney injury is a common issue in patients receiving ECMO treatment,with reported incidence rates ranging from 70%to 85%.[1]To maintain the balance of fluids and electrolytes in patients,continuous renal replacement therapy(CRRT)is frequently employed.

Shikonin protects mitochondria through the NFAT5/AMPK pathway for the treatment of diabetic wounds

BACKGROUND Shikonin is a natural remedy that is effective at treating diabetic wounds.NFAT5 is a potential therapeutic target for diabetes,and mitochondrial function is essen-tial for wound healing.However,the relationship among Shikonin,NFAT5,and mitochondrial function has not been thoroughly studied.Here,we offer new per-spectives on the advantages of shikonin for managing diabetes.AIM To assess the therapeutic mechanism of shikonin in diabetic wounds,its rela-tionship with NFAT5,and its protection of mitochondrial function.METHODS Hypertonic cell and diabetic wound mouse models were established.NFAT5 expression was measured through western blotting and immunofluorescence,in vivo and in vitro.Mitochondrial function was evaluated using reactive oxygen species(ROS)detection and JC-1 and Calcein AM dyes.Mitochondrial structures were observed using transmission electron microscopy.The NFAT5/AMPK pathway was analyzed using a transfection vector and an inhibitor.The effect of shikonin on cells under hypertonic conditions via the NFAT5/AMPK pathway was assessed using western blotting.RESULTS Shikonin treatment preserved HaCaT cell viability,while significantly reducing cyclooxygenase-2 expression levels in a high-glucose environment(P<0.05).Additionally,shikonin maintained mitochondrial morphology,enhanced membrane potential,reduced membrane permeability,and decreased ROS levels in HaCaT cells under hyperosmolar stress.Furthermore,shikonin promoted wound healing in diabetic mice(P<0.05).Shikonin also inhibited NFAT5,in vivo and in vitro(P<0.05).Shikonin treatment reduced NFAT5 expression levels,subsequently inhibiting AMPK expression in vitro(P<0.05).Finally,shikonin inhibited several key downstream molecules of the NFAT5/AMPK pathway,including mammalian target of rapamycin,protein kinase B,nuclear factor kappa-light-chain-enhancer of activated B cells,and inducible nitric oxide synthase(P<0.05).CONCLUSION Shikonin protects mitochondria via the NFAT5/AMPK-related pathway and enhances wound healing in diabetes.

Streptococcus anginosus in the development and treatment of precancerous lesions of gastric cancer

The microbiota is strongly association with cancer.Studies have shown significant differences in the gastric microbiota between patients with gastric cancer(GC)patients and noncancer patients,suggesting that the microbiota may play a role in the development of GC.Although Helicobacter pylori(H.pylori)infection is widely recognized as a primary risk factor for GC,recent studies based on microbiota sequencing technology have revealed that non-H.pylori microbes also have a significant impact on GC.A recent study discovered that Streptococcus anginosus(S.anginosus)is more prevalent in the gastric mucosa of patients with GC than in that of those without GC.S.anginosus infection can spontaneously induce chronic gastritis,mural cell atrophy,mucoid chemotaxis,and heterotrophic hyperplasia,which promote the development of precancerous lesions of GC(PLGC).S.anginosus also disrupts the gastric barrier function,promotes the proliferation of GC cells,and inhibits apoptosis.However,S.anginosus is underrepresented in the literature.Recent reports suggest that it may cause precancerous lesions,indicating its emerging pathogenicity.Modern novel molecular diagnostic techniques,such as polymerase chain reaction,genetic testing,and Ultrasensitive Chromosomal Aneuploidy Detection,can be used to gastric precancerous lesions via microbial markers.Therefore,we present a concise summary of the relationship between S.anginosus and PLGC.Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S.anginosus on PLGC.

Potential mechanism of teneligliptin in the treatment of diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM),a complication of diabetes,poses a significant threat to public health,both its diagnosis and treatment presents challenges.Teneligliptin has promising applications and research implications in the treat-ment of diabetes mellitus.Zhang et al observed the therapeutic effect of tenelig-liptin on cardiac function in mice with DCM.They validated that teneligliptin’s mechanism of action in treating DCM involves cardiomyocyte protection and inhibition of NLRP3 inflammasome activity.Given that the NLRP3 inflammasome plays a crucial role in the onset and progression of DCM,it presents a promising therapeutic target.Nevertheless,further clinical validation is required to ascertain the preventive and therapeutic efficacy of teneligliptin in DCM.

Recent efficacy and long-term survival of Astragalus polysaccharide combined with gemcitabine and S-1 in pancreatic cancer

BACKGROUND Pancreatic cancer is a highly malignant tumor with a rapid progression rate and a high susceptibility to infiltration and metastasis.Astragalus polysaccharide(APS),a pure Chinese medicine preparation primarily made from the traditional Chinese herb Astragalus,plays a positive role in the treatment of many malignant tumors.AIM To explore the recent efficacy of APS combined with gemcitabine plus tegafur gimeracil oteracil potassium capsule(S-1)(GS)regimen in the treatment of pancreatic cancer and assess its effect on the immune function and long-term survival of patients.METHODS A total of 97 patients who were diagnosed with pancreatic cancer and received GS chemotherapy at The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)from March 2021 to December 2021 were included in the retrospective analysis.Among them,41 patients received APS combined with GS chemotherapy,and 56 patients received GS chemotherapy only.The recent efficacy,immune function,adverse reactions,and long-term survival were compared among these patients.RESULTS After 4 cycles of treatment,the objective response rate of patients receiving the combined therapy of APS and GS was 51.22%,and the disease control rate(DCR)was 56.10%,higher than those of patients receiving the monotherapy with GS alone(30.36%and 35.71%,respectively).Besides,the percentages of CD3+T cells(50.18%±9.57%)and CD4+T cells(31.52%±5.33%)in the peripheral blood of patients receiving the combined therapy of APS and GS were higher compared with those treated with GS regimen alone[(44.06%±8.55%)and(26.01%±7.83%),respectively].Additionally,the incidences of leukopenia,thrombocytopenia,and fatigue in patients receiving the combined therapy of APS and GS were significantly lower than those in patients receiving the monotherapy of GS alone(17.07%,9.76%,31.71%vs 37.50%,28.57%,60.71%).Moreover,the median survival time of patients receiving the combined therapy of APS and GS was 394 days,significantly longer than that of patients receiving the mono-therapy of GS alone(339 days)(hazard ratio:0.66;95%CI:0.45-0.99;P=0.036).All these differences were statistically si-gnificant(P<0.05).CONCLUSION The combined therapy of APS and GS improved the recent efficacy and long-term survival of patients with pancreatic cancer and alleviated chemotherapy-induced immune suppression and adverse reactions.

Influence of the continuing COVID-19 epidemic on sleep quality and psychological status of healthcare workers in private institutions

BACKGROUND On January 22,2020,Macao reported its first case of coronavirus disease 2019(COVID-19)infection.By August 2021,the situation had escalated into a crisis of community transmission.In response,the government launched a recruitment campaign seeking assistance and services of healthcare workers(HCWs)from the private sector throughout Macao.These participants faced concerns about their own health and that of their families,as well as the responsibility of maintaining public health and wellness.This study aims to determine whether the ongoing epidemic has caused them physical and psychological distress.AIM To examine the influence of COVID-19 on the sleep quality and psychological status of HCWs in private institutions in Macao during the pandemic.METHODS Data were collected from December 2020 to January 2022.Two consecutive surveys were conducted.The Pittsburgh Sleep Quality Index(PSQI)scale,Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were employed as investigation tools.RESULTS In the first-stage survey,32%of HCWs experienced a sleep disorder,compared to 28.45%in the second-stage survey.A total of 31.25%of HCWs in the first-stage survey and 28.03%in the second had varying degrees of anxiety.A total of 50.00%of HCWs in the first-stage survey and 50.63%in the second experienced varying degrees of depression.No difference in PSQI scores,SAS scores,or SDS scores were observed between the two surveys,indicating that the COVID-19 epidemic influenced the sleep quality and psychological status of HCWs.The negative influence persisted over both periods but did not increase remarkably for more than a year.However,a positive correlation was observed between the PSQI,SAS,and SDS scores(r=0.428-0.775,P<0.01),indicating that when one of these states deteriorated,the other two tended to deteriorate as well.CONCLUSION The sleep quality,anxiety,and depression of HCWs in private institution in Macao were affected by the COVID-19 epidemic.While these factors did not deteriorate significantly,the negative effects persisted for a year and remained noteworthy.

Hotspots and research trends of Piwi-interacting RNAs from 2006 to 2023 based on bibliometric analysis

Background:Piwi-interacting RNAs(piRNAs)are a type of non-coding RNAs,initially identified in germ cells in 2006,known to bind to the Piwi family proteins.Accumulating studies indicate their importance in genome stability,epigenetics regulation,germ cell differentiation,and tumor development.Despite growing interest in piRNA research,there is a lack of comprehensive bibliometric studies on the subject.This study aims to analyze piRNA research trends from 2006 to 2023.Methods:The literature regarding piRNA was sourced from the Web of Science on April 25,2023.VOSviewer,CiteSpace and a bibliometric online website(https://bibliometric.com/app)were employed to perform bibliometric analysis.Network maps were constructed to evaluate the collaborations among countries,institutions,authors,journals,references,keywords,and research hot pots.Results:In this study,2549 literature were published across 464 countries and 6921 institutions,comprising 2010 articles and 539 reviews.The United States led in publication output(n=1011,39.66%),followed by China(635,24.91%).The University of Tokyo had the most publications among all institutions(n=100,3.92%),followed by the Chinese Academy of Sciences(n=86,3.37%).Among 631 published journals,Nucleic Acids Research was the most published journal(n=83,3.26%).Siomi Mikiko C published the most articles(n=58),with Aravin Alexei A as the most co-cited author.Analysis of term co-occurrence unveiled three highly interconnected clusters,including“piRNA biogenesis and function”,“cancer and regulation”,as well as“protein and species”.The research focus has transferred from male reproductive development to tumor progression.Conclusion:This bibliometric analysis offered a thorough overview of the current state of piRNA research,deepening understanding of the progress in this field over the last 17 years and providing a valuable reference for scholars engaged in piRNA studies.

Tanyu Tongzhi formula attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+) monocyte differentiation

Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.

Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis

Objective: To discuss the expression of long noncoding RNA TUG1 (IneRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Methods: Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of IncRNA-TUG I in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between IncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using IncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after IncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western -blot test. Results: The expression level of lneRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P<0.05) and the high expression level of IncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (/'<0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by IncRNA-TUG1 specific siRNA (P<0.05). The results of qRT-PCR and western -blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after IncRNA-TUG1 was silenced (P<0.05). Conclusions: IncRNA-TUG1 shows an up -regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. IncRNATUGI can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.

R-I subtype single right coronary artery with congenital absence of left coronary system: A case report

BACKGROUND Isolated single coronary artery is a rare congenital anomaly.R-I subtype single coronary artery is even rarer.In this subtype,a very large right coronary artery extends in the coronary sulcus to the anterior base of the heart where it produces the left anterior descending coronary artery.Currently,only a few case reports are available in the literature for this anomaly.CASE SUMMARY Here,we report the case of a 62-year-old woman who presented to the cardiology clinic with decreased exercise tolerance and poor blood pressure control.The patient underwent coronary angiography(CAG)and emission computed tomography(ECT).CAG images revealed a single gigantic right coronary artery(R-I type)arising from the right coronary sinus with branches supplying the left coronary territory.The ECT results confirmed myocardial ischemia at the location of the absent left coronary artery.The ECT findings confirmed that ischemia was consistent with the vascular loss location in CAG images.In such anomalies,there is a compensatory widening of the coronary artery lumen.Medical treatment was administered,and the patient was discharged.CONCLUSION Isolated single coronary arteries are associated with ischemia and potentially fatal acute coronary events.Hence,controlling risk factors is critical.

Unusual magnetic resonance imaging findings of brain and leptomeningeal metastasis in lung adenocarcinoma:A case report

BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor mutations.However,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.CASE SUMMARY We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance imaging.Surgical and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local leptomeninges.CONCLUSION This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with LM.Radiologists should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.

Curcumin attenuates iron-overloaded stress to macrophages via up-regulation of SOD and Nrf2

Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammonium citrate was added to the macrophage cell line(RAW264.7)to establish an iron-overloaded macrophage model.Cell counting kit 8 assay was used to detect cell viability.Superoxide dismutase,reactive oxygen species,malondialdehyde,and apoptosis were performed to analyze the severity of cellular oxidative damage.In addition,quantitative real-time polymerase chain reaction and western blot were used to detect the expression of nuclear factor erythroid 2-related factor 2.Results:The result showed that iron overload of macrophage was visualized by incubating in 40μM ferric ammonium citrate for 24 h.The curcumin significantly reversed the iron overload-induced apoptotic cells at low(10μM)and middle(20μM)concentrations.Additionally,the levels of malondialdehyde and reactive oxygen species activity in the groups of curcumin at low(10μM)and middle(20μM)concentrations were significantly decreased,while superoxide dismutase activity was obviously increased compared with that of the ferric ammonium citrate group alone.Finally,we found that low(10μM)and middle(20μM)dose curcumin up-regulated nuclear factor erythroid 2-related factor 2 expression at mRNA and protein levels compared with the ferric ammonium citrate group alone.Conclusion:Curcumin reduces iron-overloaded stress in macrophages by activating nuclear factor erythroid 2-related factor 2 and enhancing the superoxide dismutase activity,thereby protecting cell apoptosis.

Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

Background:Diabetic nephropathy(DN)is a serious complication of diabetes with rising prevalence worldwide.We aimed to explore the anti-DN mechanisms of the compound celastrol derived from the medicinal plant Tripterygium wilfordii.Methods:Celastrol-related targets were obtained from Herbal Ingredients’Targets(HIT)and GeneCards databases.DN-related targets were retrieved from GeneCards,DisGeNET,and Therapeutic Targets Database(TTD).A Protein-protein interaction(PPI)network was established using the Search Tool for the Retrieval of Interacting Genes(STRING)database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using ClusterProfiler.The cytoHubba plugin was used to select the top 10 hub targets.Molecular docking was performed employing PyMOL and AutoDock software.Cell counting kit-8(CCK-8)and flow cytometry assays were used to detect the viability and apoptosis of NRK-52E cells,respectively.The mRNA expression levels of mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),and AKT serine/threonine kinase 1(AKT1)in NRK-52E cells were assessed using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We obtained sixty-six overlapping targets of celastrol and DN.GO and KEGG analyses demonstrated that the core targets of celastrol and DN were mainly involved in the inflammatory and immune response,oxidative stress,advanced glycation end products(AGEs)and their receptors(RAGEs)(AGE-RAGE),TNF,interleukin 17(IL-17),and MAPK signaling pathways.Finally,based on the good binding activity with celastrol,MAPK3,TNF,and AKT1 were identified as the foremost targets of celastrol.We observed that celastrol enhanced the viability of high glucose(HG)-treated NRK-52E cells and inhibited apoptosis in the in vitro assays.Moreover,celastrol decreased the mRNA expression levels of MAPK3,TNF,and AKT1 in high glucose(HG)-treated NRK-52E cells.Conclusion:Celastrol may treat DN by targeting APK3,TNF,and AKT1 and regulating inflammatory responses and oxidative stress through the AGE-RAGE,TNF,IL-17,and MAPK signaling pathways.