May Traditional Chinese Medicine Reduce the Risk of Developing Rheumatoid Arthritis?An One-armed Prospective Study

Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of RA.Methods:This was a single-armed prospective clinical trial.All participants were recruited from a single center in Guangdong,China.Adults who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 weeks.Primary outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during observation.Secondary outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of COVID-19.During the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop RA.After 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and signs in these at-risk individuals,but it remains to be investigated in futher study to see if it might potentially reduce the risk of developing RA.Besides,for individuals at high risk to develop RA,morning stiffness and synovial enhancement in MRI might be predictive factors and warning signs.

Anti-aging Related Activities and Health Benefits of Licochalcone A:A Review

Background:Licochalcone A(LCA)is a flavonoid derived from the roots of Glycyrrhiza uralensis Fisch.ex DC and other related plants.Its natural source has been extensively used in complementary medicine,especially traditional Chinese medicine,to treat various ailments.Identified as a phenolic chalcone compound,LCA has gained significant attention in recent years due to its various pharmacological properties.Objective:The objective of this review article is to assess the anti-aging ralated pharmacological properties of LCA.Method:An exhaustive search of several scientific databases was conducted using various relevant keywords to write this review article on LCA,focusing on its therapeutic applications and anti-aging-related pharmacological activities.Some inclusion and exclusion criteria were strictly followed to retrieve updated relevant articles.Results:A collection of 292 papers were screened,and 131 were included in this review for an in-depth analysis of Licochalcone A,focusing on its anti-aging-related pharmacological activities and relevant mechanisms,and its toxicity and side effects.Moreover,the potential of LCA as a pharmacological product is discussed,emphasizing its health benefits and potential as a pharmaceutical product.Conclusion:These findings indicate that Licochalcone A is a promising natural therapeutic agent for anti-aging therapy and other ailments.

Phytochemical Screening and Evaluation of Pharmacological Potential of Baliospermum solanifolium Leaf Extract

Background:Baliospermum solanifolium is a traditional medicinal plant,locally known as“dantigaacha”from Eu-phorbiaceae family,and has been used in different diseases treatments likes helminthiasis,skin diseases,diabetes,snake-bite,and leukoderma.Objectives:Depending on the traditional uses of B.solanifolium and the lack of scientific works,we aimed to conduct some pharmacological tests on its leaves.Methods:Active constituents of B.solanifolium were assessed by qualitative screening.DPPH(2,2-diphenyl-1-picrylhydrazyl)was used for free radical scavenging assay.Behavioral change and mortality rate were used as indicators to assess the toxicity of B.solanifolium.The antidiabetic potential was evaluated by oral glucose toler-ance test(OGTT)and alpha-glucosidase enzyme inhibitory activity.In antidiarrheal activity,castor oil-induced mice were used.Antibacterial test was carried out by disk diffusion assay and MIC determination.Furthermore,analgesic activity was done by acetic acid-induced writhing method.Results:B.solanifolium contains alkaloids,carbohydrates,glycosides,flavonoids,tannis,phenolics etc.Acute toxicity test ensured the safety of the extract.In DPPH,the extract showed antioxidant activity with an IC50(con-centration needed to scavenge 50%DPPH)value of 61.65μg/mL.Total phenolic,flavonoid and tannin contents were determined as 124 mg GAE/g,440 mg QE/g and 344 mg GAE/g dried extract,respectively.In OGTT,the ex-tract reduced the blood glucose level significantly.In the alpha-glucosidase inhibitory activity,the plant showed a concentration-dependent reduction of the enzyme at IC50 of 8.53 mg/mL.In the antidiarrheal test,B.solanifolium inhibit defecation 30.69%and 53.41%at dose 250 mg/kg and 500 mg/kg,respectively.The extract also showed antibacterial activity against four bacterial strains in the disk diffusion method and minimum inhibitory concen-tration(MIC)values were 62.5μg/mL,62.5μg/mL,125μg/mL and 62.5μg/mL against four bacterial strains,independently.In analgesic activity test,the extract reduced the writhing impulse up to 48.51%at 500 mg/kg dose.Conclusion:B.solanifolium contains many active phytoconstituents which may be the possible candidates for targeting diabetes,microbial infection,diarrhea and pain in the future.

Therapeutic Benefits of Vernonia amygdalina in the Treatment of Inflammation and Its Associated Diseases

Background:In the presence of a stimulus that disrupts homeostasis,the body elicits a response known as in-flammation.The inflammatory response is expected to restore the normal functioning of the body and initiate healing where necessary.However,the persistent activity of acute inflammation results in chronic inflammation which causes adverse consequences associated with diseases such as diabetes and arthritis.In traditional medical practice,Vernonia amygdalina is used to treat several ailments such as malaria,fever,diabetes,and inflammatory conditions such as those related to pain and swelling.Objective:This review seeks to explore and discuss the therapeutic benefits of V.amygdalina in the treatment of inflammation and its associated diseases.Methods:We reviewed the scientific literature indexed in PubMed,ScienceDirect and Springer,and discussed the reported anti-inflammatory properties of V.amygdalina and its curative activity in inflammation-associated diseases.Results:A total of 30 published articles were identified describing the therapeutic effect of V.amygdalina in predominately experimental models.The anti-inflammatory properties of V.amygdalina have been linked to the presence of bioactive phytoconstituents predominantly present in the leaves of the plant.Conclusions:Multiple studies have demonstrated that the aqueous and ethanolic extracts of V.amygdalina can inhibit the production of proinflammatory cytokines and enzymes in inflammatory cells,reducing inflammation and its associated complications.We critically appraise the current evidence,and discuss the potential use of this medicinal plant in the treatment of inflammatory conditions.

The Effect of Xu’s Influenza Decoction Combined with Oseltamivir on Influenza A:A Propensity Score Matching Study

Background:The resurgence of seasonal influenza virus circulation has been seen in 2021-2022 after the tempo-rary suppression in 2020-2021.Neuraminidase inhibitors(NAIs)are widely applied in the clinical treatment of influenza A despite several limitations.Objective:To access the efficacy of Xu’s influenza decoction(XID)in combination therapy with oseltamivir for the treatment of influenza A.Methods:In this retrospective cohort study,the eligible participants were diagnosed with influenza A between June 1,2018,and May 30,2022,in the First Affiliated Hospital of Zhejiang Chinese Medical University.According to whether Xu’s influenza decoction was applied,patients were divided into two groups:treated with or without XID.Propensity score matching(PSM)was used to further adjust the covariates between groups.The primary outcome was to compare time to defervescence via K-M curves,Breslow tests,and Cox regression analysis.In Cox proportional hazards model,a univariate analysis was performed to obtain preliminary results,while a further multivariate analysis was conducted to study the independent factors that influence defervescence.Subgroup analysis was conducted according to body temperature and time from onset to admission.The secondary outcome consisted of routine blood and C-reactive protein(CRP),length of stay,and medical costs.Results:A total of 336 patients with influenza A were enrolled in this study(i.e.,163 patients in the XID+oseltamivir group;173 patients in the oseltamivir group).After 1:1 matching via PSM,230 patients meeting the criteria were included in the analysis,with 115 in each arm.The XID+oseltamivir group had shorter time to defervescence(36 h vs 44 h,P=0.011),shorter length of stay(3 days vs 4 days,P=0.018),and higher defervescence possibility(HR=1.384,95%CI:1.054-1.818).Subgroup analysis indicated that for patients during non-window period(≥48 h)with medium-grade fever(38.1℃-39℃),the XID+oseltamivir combination therapy reduced time to defervescence(P=0.04995/0.004)with a higher defervescence possibility(HR=1.524/1.683).Meanwhile,there’s no statistical significance but observable trends of the XID+oseltamivir group in the lower medical costs(3068.07 yuan vs 3120.68 yuan),the lower neutrophils%(48.53%vs 51.00%)and the higher lymphocyte%(39.83%vs 37.72%).Conclusion:The combination of XID and oseltamivir can shorten the time to defervescence and length of stay in influenza A.Its antipyretic effect is mainly reflected in the medium-grade and non-window periods.

AG8 Reduces Hypoxia-induced Triple Negative Breast Cancer Metastasis by Stemness Regulation

Background:AG8,a triterpenoid saponin isolated from Ardisia gigantifolia Stapf.,our previous studies found that AG8 inhibited the proliferation of triple negative breast cancers(TNBCs)by including ROS generation and triggering mitochondrial apoptotic pathways.Cancer stem cells(CSCs)capable of maintain relatively low levels of ROS,are vulnerable to the interference of redox state.Compounds capable of generating ROS can affect the finely balanced redox state of CSCs and have potency to selectively kill them.Objective:We selected BT-549 which is most sensitive to AG8 to further study the effects of AG8 on hypoxia-induced proliferation,metastasis and CSCs.Methods:The hypoxia condition was simulated by CoCl2 and cell viability assay of BT-549 cells was performed us-ing MTT.Stemness phenotype were identified using breast CSCs marker(CD24^(−)/low/CD44^(+))and mammosphere formation assay.Cell motility was determined via the wound healing assay and transwell migration.Protein levels of HIF1-α,Oct-4,SOX-2,c-MYC were tested by western blotting.Results:In this study,AG8 showed significant cytotoxic effects on BT-549 triple negative breast cancer cells,but the effects were impaired by HIF1 activation.AG8 inhibited the hypoxia-induced migration and invasion of BT-549 cells.Further studies revealed that hypoxia-induced increases of CD44^(+)CD24^(−)/low and mammosphere population were significantly inhibited by AG8 dose-dependently.Moreover,AG8 decreased the Oct-4 and SOX-2 protein expression without affecting HIF1-αand c-MYC.AG8 significantly inhibited BT-549 xenograft tumors growth in BALB/c nude mice comparing with that of the control group.Conclusion:In summary,AG8 inhibited hypoxia-induced cell migration and invasion through stemness regula-tions,indicating novel mechanisms for the antitumor effects of AG8 against triple negative breast cancer.

Reviving Fertility:Phytochemicals as Natural Allies in the Fight against Non-genetic Male Infertility

Background:Male infertility poses a growing challenge to the healthcare system,with its prevalence on the rise.Unhealthy lifestyle,food,and addictions such as smoking,alcoholism,etc.accelerate the occurrence.While several approaches are being investigated to prevent and treat this condition,each therapeutic approach has its drawbacks.Traditional medications continue to play a crucial role in the healthcare system.In recent years,there has been a shift towards determining the efficacy of phytochemicals(or,herbal drugs)as remedies.Objective:To evaluate the effect of various herbs,plant,metabolites,or a part of plant in management of non-genetic male infertility.Methods:The male infertility-associated keywords were searched in PubMed,excluding those non-English writen papers.A total of 146 pertinent and closely connected records were included for full reading and inclusion in the systemic evaluation.Results:The manuscript focuses on individual herbal drug components,their active ingredients,their role in improving the condition and quality of life,and decreasing the prevalence of male infertility.Conclusion:Herbal medicinal plants show promising outcomes to treat male infertility.Herbal alternatives are appealing and have regained popularity.The future holds promise for some of these herbal treatments to advance with many showing improved outcomes in males with infertility issues.

A Comprehensive Review on Preclinical Safety and Toxicity of Medicinal Plants

Background:Globally,80%people use plant-derived products for treating or preventing diseases.One prevalent perception about medicinal plants is that they are safe and devoid of adverse effects.However,approximately 1,50,000 plants contain toxic substances.Objective:The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclin-ical models by oral route.Methods:Detail studies were searched from databases including PubMed and Google Scholar.A manual reference screening of the selected studies was done to identify relevant articles,with no language restriction being imposed at the time of searching.Results:The studies included were performed in rodents,and the test substances were administered orally.Our search revealed 33 widely used plants or products with significant toxicity,and phytochemicals from these plants have been summarized.Through a systematic review,we identified a plethora of medicinal plant extracts reporting safety and toxicity concerns.Conclusion:In the future,preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety assessment.Finally,the interaction of herbs with com-monly used/over-the-counter drugs in terms of the latter’s metabolic profile should be undertaken.

GSZ Formula Enhances Sleep Quality:Exploring Its Active Ingredients and Mechanism Using a Network Medicine Approach

Background:Sleep is essential for maintaining human health,and insomnia is a widespread problem.Traditional Chinese medicine(TCM)has been used for centuries to treat sleep disorders,with fewer reported side effects compared to conventional treatments.Objective:This study seeks to investigate the sleep-promoting effects of the GSZ formula,which comprisesγ-aminobutyric acid(GABA),Schisandrae Chinensis Fructus(Wuweizi in Chinese),and Ziziphi Spinosae Semen(Suanzaoren in Chinese).In addition,this study aims to explore the active ingredients and potential mechanisms underlying the sleep-enhancing effects of the formula.Methods:The impact of GSZ on sleep was evaluated using two models,the complete sleep model and the sub-threshold sleep model.Mice were randomly divided into five groups and orally administered GSZ solution(0.33 g/kg/day or 0.99 g/kg/day),positive drug diazepam(2.50 mg/kg)or a control solution for 30 days.Hypno-sis model was established in mice using pentobarbital sodium.Sleep duration and incidence were measured by recording when the righting reflex of mice disappeared for more than 1 min.GABA and dopamine(DA)levels in mouse brain tissue were measured using ELISA kits.The ingredients of the GSZ formula were identified using mass spectrometry,and the targets of these ingredients and disease-related genes were retrieved from public databases.A network medicine approach was used to calculate the shortest path between ingredient targets and disease-related proteins.The expression levels of potential proteins,such as Akt,p-Akt,GSK-3β,and p-GSK-3β,were analyzed using Western blotting based on the predicted results.Results:GSZ significantly prolonged sleep duration and enhanced the sleep rate in mice(P<0.05).Furthermore,it elevated GABA levels and reduced DA levels in the mouse brain(P<0.05).Network medicine analysis suggested that GABA,stearic acid,genistin,and coumestrol may be the most crucial active ingredients for sleep improve-ment.Western blotting analysis demonstrated that GSZ modulated the protein expression levels of p-Akt/Akt and p-GSK-3β/GSK-3β(P<0.05).Conclusion:Our study demonstrated that the GSZ formula could improve sleep,with key ingredients likely being GABA,stearic acid,genistin,and coumestrol.The mechanism might involve the regulation of the Akt/GSK-3βpathway,as revealed by the network medicine analysis and experimental validation.Our current new findings shed light on the potential mechanisms underlying the sleep-enhancing effects of the GSZ formula,which could provide experimental evidence to develop innovative treatments for insomnia.

An in vitro Anti-urolithiasis Activity of a Herbal Formulation:Spinacia oleracea L.and Coriandrum sativum L.

Background:Hard mineral and acid salt deposits that clump together in concentrated urine are known as kidney stones.A complicated chain of physicochemical events,including hyper saturation,nucleation,growth,aggrega-tion,and retention in the urinary tract,leads to urolithiasis,the third most prevalent urinary tract issue.Numerous traditional medications and therapies are less successful in treating urolithiasis and frequently cause recurrences.Objective:The present study is focused on evaluating the anti-urolithiasis activities of the polyherbal formulation prepared from Spinacia oleracea L.and Coriandrum sativum L.seeds.Methods:To evaluating the anti-urolithiasis activities of the polyherbal formulation prepared from S.oleracea and C.sativum seeds against oxalate crystals by employing an in vitro inhibition,aggregation,and nucleation assay,employing a spectrophotometer followed by microscopic observation,and further monitored by egg semiperme-able membrane model,using cystone as a standard drug.Results:In the present work,the alkaloids,glycosides,flavonoids,glycosides,phenols,saponins,steroids,tannins,terpenoids,and triterpenoids were found in the extracts of S.oleracea and C.sativum.The in vitro assays in the present study clearly indicated that all the mixture extracts readily prevented crystal nucleation,growth and ag-gregation.The aqueous extract of the mixture inhibited significant inhibitory potential against the crystallization process.Conclusion:It can be said that the phyto-constituents enriched homemade preparation possibly will be used as a medication for the management of kidney stones by dissolving the oxalate stone in the kidney.

Electroacupuncture Alleviates HIF1-α-mediated Early Mitophagy in Spinal Cord Injury

Background:The inhibitory microenvironment around spinal cord injury(SCI)severely restricted functional repair after injury.Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment.Hypoxia-inducible factor1α(HIF1-α)can mediate mitochondrial autophagy in neurodegenerative diseases,but the mechanisms are complex and diverse,which need to be further elucidated.Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury,promote long-term neurological function recovery in SCI patients,but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown.Objective:Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture.Methods:Following the successful construction of an SCI model of Sprague-Dawley rat utilizing a modified Allen method,electroacupuncture intervention was performed at T9 and T11 Jiaji acupoint(EX-B2),with further molecular biology and morphology examined by perfusion.To observe the effect of HIF1-α on local damage repair,the stereotypic injection of Hif1a knockdown virus was performed,and the changes of mitophagy in damaged local area was detected employing Western blotting,real-time fluorescence quantitative PCR,immunofluorescence,transmission electron microscopy and Nissl staining.Results:HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury.Elec-troacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury,reduce cell apoptosis and injury area,promote neuronal survival.Conclusion:Electroacupuncture may serve as a promising strategy for spinal cord injury treatment,by alleviating HIF1-α mediated early mitochondrial autophagy.

Diuretic Activity of Ethanol Extract of Piper attenuatum Leaves Might Be Due to the Inhibition of Carbonic Anhydrase Enzyme:An in vivo and in silico Investigation

Background:Ayurvedic system of medicine is well established for prevention and treatment of renal problems.There are vast number of medicinal plants mentioned in Ayurvedic system of medicine,including Piper attenuatum Buch.-Ham.ex Miq.,which has been known to exhibit diuretic properties.Objective:To investigate possible mechanism and diuretic activity of ethanol extract of P.attenuatum leaves.Methods:Present study reports an in vivo diuretic activity of ethanol extracts of P.attenuatum leaves.Twenty-four Sprague-Dawley male rats were deprived from food and water for 20 h,followed by being divided into four groups to receive normal saline,Furosemide,and two doses of the ethanol extract,respectively.Further,the ethanol extract were subjected for prelimnary phytochemical screening test,and analytical investigation was performed via high-performance thin-layer chromatography(HPTLC),followed by effectiveness exploration of putative bioactive compounds from P.attenuatum against human carbonic anhydrase(hCA)enzyme using molecular docking tool.Results:During phytochemicals screening,several groups of compounds such as amides,terpenoids,proteins,flavonoids,and glycosides have been identified.Further,HPTLC reveals presence of carbohydrates,proteins,amino acids,steroids,alkaloids,flavonoids,tannins,glycosides,and terpenoids.Significant diuretic action was revealed for both 200 mg/kg bw and 400 mg/kg bw of ethanol extract of P.attenuatum leaves.Interestingly,molecular docking analysis demonstrated greater binding affinity of compounds such as Cepharadione A,Nor-cepharadione B,Galbelgin,Crotepoxide,and Pipoxide chlorohydrin out of total 23 studied compounds against hCA isoforms(a key biomarker for diuretic)and score is comparable with standard drug Acetazolamide.Conclusion:It was concluded from the present studies that ethanol extract of P.attenuatum leaves exhibits signifi-cant diuretic activity.The activity may be correlated due to the presence of Cepharadione A,Norcepharadione B,Galbelgin,Crotepoxide,and Pipoxide chlorohydrin as key component responsible for inhibition of hCA isoforms.

Efficacy of TCM Fumigation Using Dampness-and-cold-dispelling Formula Combined with Methotrexate and Leflunomide Treating Rheumatoid Arthritis with Cold-dampness Bi Syndrome

Background:Rheumatoid arthritis(RA),a chronic autoimmune disease,has a high incidence and disability rate,causing patients significant discomfort.Although several medicines can be effective,they are also associated with significant adverse effects.In contrast,fumigation as one of the most often used traditional Chinese medicine(TCM)external therapy has shown both efficacy and safety with less side effect.In light of this,we comple-ment western medicine treatment with TCM fumigation therapy to improve patients’clinical efficacy,alleviate symptoms,and improve prognosis.Objective:To investigate the therapeutic effect of TCM fumigation and modern medicine combined therapy in treating RA patients with cold-dampness Bi syndrome.Methods:A single-center,randomized,controlled study was designed.From January 2022 to December 2022,a total of 60 RA patients with cold-dampness Bi syndrome were enrolled in the study.The control group(30 cases)received conventional modern medicine treatment with methotrexate for 4 weeks,while the observation group(30 cases)for 4 weeks received a combination of TCM fumigation treatment and conventional modern medicine.The effects of the two groups were comprehensively compared,including the changes in TCM symptom scores and laboratory indicators,as well as the use of visual analogue scale(VAS)and health status rating scale(HAQ)before and after treatment.Results:The total effective rate of the observation group was 93.3%,which was significantly higher than that of the control group,which is 70%(P<0.05).Before treatment,there were no significant differences in joint functional activity,pain visual analogue scale(VAS),health assessment questionnaire(HAQ-DI)and laboratory indexes between the two groups(P>0.05).After treatment,each group compared to their initial condition,respectively,showed major improvement of joint functional activity and significantly decreased VAS,HAQ-DI,and RA-related biomarkers(P<0.05);inter-group comparison of these indicators showed significanty further enhanced effect of TCM fumigation combined therapy on the RA-related biomarkers and joint functional activity of patients(P<0.05),yet the control group receiving only modern medicine showed better results of the VAS and HAQ-DI.Conclusion:The TCM fumigation combined therapy is effective to treat RA patients with cold-dampness Bi syn-drome,and to enhance their life quality,improving the joint function,and reducing inflammation.

Phytochemical Loaded Nanovehicles of Biopolymer for Breast Cancer:A Systemic Review

Background:Breast cancer is one of the most common malignancies affecting women worldwide,emphasizing the need for effective therapeutic strategies.Phytochemicals derived from plants have gained significant attention due to their potential anticancer properties.Objective:This review aims to comprehensively assess the existing literature on using phytochemical-loaded for-mulations as a therapeutic approach for breast cancer.By analyzing the available evidence,we aim to determine the potential benefits and limitations of these formulations in terms of their anticancer activity,bioavailability,and safety.Methods:A systematic search of relevant databases was conducted to identify studies investigating phytochemical-loaded formulations in the context of breast cancer treatment.The inclusion criteria encompassed clinical trials,preclinical studies,and in-vitro experiments that reported using phytochemicals in various formulations for breast cancer treatment.Data extraction was performed to ensure the reliability and validity of the included studies.Results:The review highlights the diverse range of phytochemicals used in different formulations for breast cancer treatment.Findings suggest that these formulations exhibit promising anticancer effects by targeting mul-tiple signaling pathways in breast cancer progression,including cell proliferation,apoptosis,angiogenesis,and metastasis.Moreover,various delivery systems,such as nanoparticles,liposomes,and micelles,have enhanced phytochemicals’bioavailability and targeted delivery.Conclusion:Phytochemical-loaded formulations hold immense potential as a therapeutic approach for breast cancer treatment.The reviewed evidence indicates their ability to inhibit tumor growth,enhance chemotherapy effectiveness,and reduce adverse effects.However,further research is warranted to optimize the formulation strategies,investigate the long-term safety profiles,and conduct large-scale clinical trials to establish their efficacy and applicability in clinical settings.These findings contribute to developing novel phytochemical-based therapies for breast cancer,offering new avenues for personalized and targeted treatment options.

Notoginsenoside R1 Protects against Diabetic Nephropathy through TXNIP-NLRP3 Signaling Pathway

Background:Diabetic nephropathy(DN)is a microvascular complication of diabetes mellitus(DM).DN results from many factors,including changes in glomerular hemodynamics,oxidative stress and inflammation,and in-terstitial fibrosis and tubular atrophy.Panax notoginseng,a commonly used Chinese medicine,has been used in the treatment of kidney disease.Notoginsenoside R1(NGR1),the main compound isolated from P.notoginseng,has been reported to have a renoprotective role in DN.However,the therapeutic effect and mechanism of NGR1 in DN remain unclear.Objective:The present study aimed to investigate the therapeutic effect and mechanism of NGR1 in DN.Methods:In this study,mouse podocytes(MPC-5 cells)and db/db mice were used to investigate the effect of NGR1 on DN in vitro and in vivo,respectively.Blood glucose,renal function,inflammatory factors,and PI3K/AKT-Nrf2-NLRP3 signaling pathway proteins were assessed.Results:The study results indicated that NGR1 reversed cell viability induced by high glucose(HG,30 mM).The related mechanism results showed that NGR1 decreased oxidative stress by inhibiting reactive oxygen species(ROS)level and upregulating the expression of Nrf2,NQO1,and HO-1 via TXNIP targeting.In addition,NLRP3 inflammasome and PI3K/AKT were engaged in NGR1-based protection against HG-stimulated podocytes.In db/db mice,NGR1 significantly decreased blood glucose,urine protein,urine output,blood urea nitrogen,and other parameters as well as reversed kidney injury by inhibiting oxidative stress and proinflammatory response.Conclusion:Taken together,this study revealed that NGR1 exerted a significant therapeutic effect on DN both in vitro and in vivo via a mechanism related to the TXNIP-Nrf2 pathway and NLRP3 inflammasome,suggesting that NGR1 is a potential therapeutic option for DN.

Pathological Mechanism of “Phlegm, Blood stasis, Toxin ”in a Rabbit Model of Carotid Atherosclerosis Based on Gut Microbiota-host Metabolism Interactions

Background:In Traditional Chinese Medicine(TCM)theory,"phlegm,blood stasis and toxin"are the pathogenesis of carotid atherosclerosis(CAS).The rabbit carotid atherosclerosis(CAS),which is induced by high-cholesterol diet combined with carotid artery balloon injury,is a classic model for studying CAS.Many studies indicate that gut microbiota and host metabolic disorders are involved in the pathogenesis of rabbit CAS.However,the TCM pathological features and syndromes of this classic rabbit CAS model have not been reported.Objective:To explore the pathogenesis of the rabbit CAS model and its TCM syndrome types from the perspective of"phlegm,blood stasis,and toxin".Methods:Twelve male New Zealand white rabbits were randomly divided into NC group and CAS group according to their body weight,followed by feeding of basic feed and a 1%high cholesterol diet,respectively.After two weeks,the rabbits in the CAS group underwent common carotid artery(CCA)balloon injury,while the rabbits in the NC group underwent only CCA separation without balloon injury.The two groups received differential feed postoperatively for six more weeks,after which,changes in lipids,hemorheology,inflammation,oxidative stress,and CAS phenotypes were analyzed.In addition,the colon contents and serum were collected for 16S rRNA sequencing and ^(1)H-NMR metabonomic analysis.Results:The CAS rabbits were observed to form noticeable abnormalities in lipid metabolism and blood rhe-ology,a sharp increase in oxidative stress levels,excessive release of inflammatory factors and apparent CAS plaque formation.Furthermore,10 specific gut microbiota(such as Akkermansia muciniphila,Barnesiellaceae and Faecalibacterium)and 14 characteristic metabolites(such as trimethylamine oxide,acetic acid and L-carnitine)were identified in the CAS rabbits,which were significantly related to the CAS phenotypes.The pathway func-tion analysis showed that the gut microbiota and its metabolites mainly affected cholesterol metabolism,energy metabolism,inflammation and oxidative stress.Conclusion:The rabbit CAS model conforms to the“phlegm,blood stasis and toxin damage”theory.The gut microbiota and host metabolic disorders of the CAS rabbits interact and promote internal and external toxins,aggravating the progression of CAS.Our study provided experimental evidence for the application of this model in the TCM-based research of CAS.

Carya cathayensis Leaf Extract Exerts Estrogenic Effects on Hepatic Lipogenesis and Adipocytes Differentiation in Ovariectomized Rats Fed Normal or High-fat Diets

Background:Our previous in vitro study has shown that total flavonoids from the leaves of Carya cathayensis exert estrogenic activities by promoting the expressions of ER𝛼and ER𝛽.C.cathayensis leaf extract(CCE)was rich in flavonoids.Oral administration of CCE reduced the serum lipids and hepatic lipids,alleviated liver steatosis in ovariectomized rats.Objective:To investigate whether CCE has estrogenic effects on reproductive tissue and influences lipid metabolism in ovariectomized rats,and whether CCE has a direct effect on regulation of lipid synthesis and/or oxidation and adipocyte differentiation of ovariectomized(OVX)rats.Methods:Female Sprague-Dawley rats were ovariectomized and treated with CCE or estradiol in combination with a normal diet(ND),a high-fat diet(HFD)for 8 weeks.Histological analysis of uterus were performed and the lipid metabolism-related enzyme activity were examined.Expression of liver lipogenesis-related genes,adipocyte differentiation-and fat accumulation-related genes and protein were measured.Rusults:Ovariectomy accelerated the uterine atrophy,development of dyslipidemia and hepatic steatosis,which were effectively mitigated by CCE supplementation.CCE significantly elevated ovariectomy-induced reduction in the cross-section area of the uterus and uterine glands.Compared with the OVX group,CCE increased the activities of lipoprtein lipase(LPL)and hepatic lipase(HL),decreased the hepatic mRNA expressions of Fas,Srebf1,Sla2a2,and increased Ppar𝛼expressions at the mRNA levels under both ND and HFD conditions.CCE also decreased the Pck1 and G6pc mRNA expressions under HFD conditions,and show no significant effects on Hmgcr.The expressions of SREBF1,CEBPA and VEGF at the protein level were effectively regulated by CCE supplementation.Conclusion:CCE effectively alleviated ovariectomy-induced dyslipidemia and visceral fat accumulation by mod-ulating hepatic lipogenesis and adipocyte differentiation.Furthermore,CCE exhibited estrogenic activity for the prevention of postmenopausal fatty liver.

Anticonvulsant Effect of Xingnaojing Injection on Acute Seizure Models in Mice

Background:Epilepsy is characterized by acute recurrent seizures.The control of seizures is largely hampered by the tolerance to current anti-seizure drugs.Complementary anti-convulsant pharmacotherapies are urgently needed.Objective:Here,we aimed to investigate the anti-convulsant effects of Xingnaojing Injection(XNJ)which is an approved Traditional Chinese Medicine injection on different acute seizure models in mice.Methods:The effects of XNJ were tested on the maximal electroshock(MES),pentylenetetrazol(PTZ)and kainic acid(KA)acute seizure models.Also,whether XNJ can directly inhibit hippocampal neuronal firings were exam-ined by in vitro electrophysiology.Results:XNJ could shorten the durations of generalized tonic-clonic seizures in the MES model.It also significantly prolonged the latencies to generalized myo-clonic seizures in the PTZ model.In the KA model,XNJ showed various efficacies including inhibiting the seizure stages,prolonging the latency to the occurrence of the first seizures or generalized seizures,shortening the seizure durations,decreasing the numbers of generalized seizures.In vitro electrophysiological recordings further verified XNJ directly inhibited both the spontaneous and evoked action potentials of hippocampal pyramidal neurons,but did not influence the excitatory or inhibitory synaptic transmissions.Conclusion:These findings proposed XNJ as an alternative anti-convulsant pharmacotherapy for controlling acute epileptic seizures.

Evaluation of the Antidiabetic Activity and Toxicological Properties of Hippocratea Velutina (Afzel.)

Background:Hippocratea velutina(HV)is a novel plant folklorically used for lowering blood glucose,hence a potential source of new antidiabetic medication.Objective:The study evaluated the anti-diabetic potentials of the methanol extract of Hippocratea velutina leaf and its toxicity profile in mice and rats.Methods:Acute and subacute toxicity tests of the plant extract were carried out by using a modified OECD guideline.Its antidiabetic activity in streptozotocin-induced diabetic rats at 50,150,and 300 mg/kg for 28 days was assayed,while glibenclamide(5 mg/kg)and distilled water were the positive and negative controls,respectively.Histopathological examination of vital organs was also carried out.Results:Preliminary phytochemical screening of the leaf extract showed the presence of tannins,flavonoids,saponins,alkaloids,terpenoids,deoxy-sugars,and anthraquinones in HV.The extract had LD 50 greater than 2000 mg/kg in mice.It had no toxic effects on the haematological and biochemical components from blood samples collected but caused significant blood glucose level reduction in normal rats at 150 and 300 mg/kg.In streptozotocin-induced diabetic rats,the extract elicited a non-dose-dependent antidiabetic effect on day seven at all the tested doses,significantly higher than glibenclamide(10 mg/kg).However,on days 14,21,and 28,the extract activity at all the tested doses and glibenclamide were comparable.The extract did not affect the liver,brain,kidney,and pancreas histology at 200 mg/kg but caused slight and severe effects on these organs at 400 and 800 mg/kg,respectively.Conclusion:The study concluded that Hippocratea velutina possessed antihyperglycaemic activity and was non-toxic at low doses but could have deleterious effects to the liver and kidney at high concentrations.

Clinical Use of COX-2 Inhibitors Containing Quinoline Heterocycle as a Selective Therapeutic Agents for Complementary Medicine

Inflammation represents an initial response of immune system and is involved in a number of biochemical inci-dents.Such incidents may multiply and further develop the provocative response.Over the past 15 years,various classes of secondary metabolites that were isolated from plant and marine sources have been described as natural cyclooxygenase(COX)inhibitors.The majority of natural COX inhibitors could be used as a selective therapeutic agent for complementary medicine and clinical applications.Currently,the inflammation is commonly treated by non-steroidal anti-inflammatory drugs(NSAIDs),several medications of which,however,have been linked to renal and gastrointestinal side effects.A variety of inhibitors of COX-2 that are selective(celecoxib,rofecoxib,valdecoxib and others)have been designed as NSAIDs mostly with enhanced stomach safety profiles.This helps to improve the compliance and functions in the geriatric patients as they have so many complications and problems associated with the diseases.The use of complementary medicine in combination with clinical therapy might give better results than medicine alone.Some disease condition like cancer which shows the COX-2 expressions could also have treatment related problems in such cases the selective inhibitors used as a complementary medicine.On the other hand,elevated cardiovascular risks have brought increasing worries about the safety of using specific inhibitors of COX-2.This current review focuses on how quinoline heterocycle was used for creation of inhibitors of COX-2 since 2009 along with its clinical significance in complementary medicine.These agents included the variety of substituents on the ring or ring attached to other heterocycles.As a result,the quinoline heterocycle will be used for creating and finding anti-inflammatory COX-2 medicines.