Integration of traditional,complementary,and alternative medicine with modern biomedicine:the scientization,evidence,and challenges for integration of traditional Chinese medicine

Traditional medicine has garnered significant global recognition,with an estimated 80%of the global population using it.Therefore,it is essential to fully understand the integration of traditional medicines into current healthcare systems.This review aims to provide a comprehensive overview of the standard process to modernize traditional medicine scientifically in the context of modern biomedicine,further termed here as“scientization”.Specifically,we aim to summarize the advancements made in understanding the efficacy,effectiveness,and underlying mechanisms of herbal medicine.We also examined the transition from experience-to evidence-based medicine during acupuncture.Furthermore,we explore the development of universal safety and quality control standards.Finally,we discuss international trade and export markets for Chinese medical products.The development and integration of traditional medicine have allowed it to further improve human health,resulting in a more comprehensive health solution for the global population.

Molecular Identification of Chinese Materia Medica and Its Adulterants Using ITS2 and <i>psbA-trnH</i>Barcodes: A Case Study on Rhizoma Menispermi

Rhizoma Menispermi, derived from the rhizoma of Menispermum dauricum DC., is one of the most popular Chinese medicines. However Rhizoma Menispermi is often illegally mixed with other species in the herbal market, including Aristolochia mollissimae Hance, which is toxic to the kidneys and potentially carcinogenic. The use of DNA barcoding to authenticate herbs has improved the management and safety of traditional medicines. In this paper, 49 samples belonging to five species, including 34 samples of M. dauricum, from different locations and herb markets in China were collected and identified using DNA barcoding. The sequences of all 34 samples of Rhizoma Menispermi are highly consistent, with only one site variation in internal transcribed spacer 2 (ITS2) of nuclear ribosomal DNA and no variations in the psbA-trnH region. The intra-specific genetic distance is much smaller than inter-specific one. Phylogenetic analysis shows that both sequences allow the successful identification of all species. Nearest distance and BLAST1 methods for the ITS2 and psbA-trnH regions indicate 100% identification efficiency. Our research shows that DNA barcoding can effectively distinguish Rhizoma Menispermi from its adulterants from both commercial and original samples, which provides a new and reliable way to monitor commercial herbs and to manage the modern medicine market.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Comprehensive reutilization of herbal waste:Coproduction of magnolol,honokiol,and β-amyrin from Magnolia officinalis residue

Herbal extraction residues(HERs)cause serious environmental pollution and resource waste.In this study,a novel green route was designed for the comprehensive reutilization of all components in HERs,taking Magnolia officinalis residues(MOR)as an example.The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients(magnolol and honokiol)originally remaining in MOR and to make MOR more accessible for hydrolysis.A metal–organic frame material MIL-101(Cr)with a maximum absorption capacity of 255.64 mg g^(-1)was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions,and 40 g L^(-1)reducing sugars were obtained with 81.8%enzymatic hydrolysis rate at 10%MOR solid loading.Finally,382 mg L-1β-amyrin was produced from MOR hydrolysates by an engineered yeast strain.In total,1 kg honokiol,8 kg magnolol,and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

Neuroinflammation attenuation effects by celastrol and PDIA3 in the amygdala, hippocampus and dorsal raphe nucleus of obese mice

Nowadays,roughly 603.7 million people are bothered by obesity[1].More seriously,obesity brings inflammation to the peripheral and central nervous system,which compromises the comorbidity of obesity,major depression[2],and cognitive deficits[3].Drug competent in the comorbidity is still lacking.In 2015,Liu et al.[4]reported celastrol(CEL)as a powerful anti-obesity agent.In our previous study.

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

A comparative study of the anti-fatigue activity of extracts from different parts of Cistanche tubulosa(Schenk)Wight

Objective:To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa(Schenk)Wight(C.tubulosa,Rou Cong Rong),focusing on central and exercise-induced fatigue in mice.This study investigated the pharmacological effects of the total oligosaccharides,polysaccharides,and phenylethanoid glycosides(CPhGs)extracted from C.tubulosa.Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue.The mice were treated with different extracts of C.tubulosa,and their effects were assessed using behavioral tests to measure exercise capacity,learning,and memory function.Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels,liver and muscle glycogen storage,and various fatigue-related biomarkers.Results: This study found that treatment with C.tubulosa extract improved exercise capacity,learning,and memory in mice.Total oligosaccharides from C.tubulosa enhanced adrenocorticotropic hormone,cholinesterase,and thyroid-stimulating hormone levels,reduced cortisol levels in central fatigue models,and ameliorated biochemical markers of exercise-induced fatigue,including lowering lactic acid,blood urea nitrogen,and malondialdehyde levels.Among the tested extracts,the total oligosaccharides showed the most comprehensive anti-fatigue effects.Conclusion: The anti-fatigue effects of C.tubulosa,particularly those of its total oligosaccharides,are pronounced in both central and exercise-induced fatigue.These effects are mediated by the regulation of neurotransmitter levels,enhancement of glycogen storage,and improvement of antioxidant enzyme activity,suggesting potential therapeutic benefits in fatigue-related conditions.

Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2

Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.

Efficacy of Pudilan Xiaoyan Oral Liquid in the treatment of pneumonia induced by drug-resistant Pseudomonas aeruginosa

Background:Pudilan Xiaoyan Oral Liquid(PDL)is a Chinese patent medicine with notable pharmacological properties,including anti-inflammatory and antibacterial effects.Drug-resistant Pseudomonas aeruginosa infection is a common and refractory bacterial infection in clinical practice.Due to its high drug resistance,it brings great challenges to treatment.This study aimed to assess the therapeutic efficacy of PDL in a murine model of pneumonia induced by drug-resistant Pseudomonas aeruginosa.Methods:Three different doses of PDL(11 mL/kg/d,5.5 mL/kg/d,2.75 mL/kg/d)were used to observe lung tissue pathology and inflammatory cytokine levels in pneumonia mouse models induced by multidrug-resistant Pseudomonas aeruginosa(MDR-PA).Additionally,the protective efficacy of PDL against mortality in infected mice was evaluated using a death model caused by MDR-PA.Finally sub-MIC concentration of levofloxacin was used to induce drug-resistant mice pneumonia model to evaluate the role of PDL in reversing drug resistance.Experimental data are expressed as mean±standard deviation.Statistical significance was determined by one-way analysis of variance followed by Tukey’s multiple-comparisons test.Results:Treatment effect of PDL on MDR-PA pneumonia:the medium and small doses of PDL can significantly reduce the lung index of multi-drug resistant bacteria infected pneumonia model mice(P<0.05),the lung index inhibition rates for these groups were 55.09%and 58.43%,and improve the degree of lung tissue lesions of mice;The expression of serum cytokines keratinocyte chemoattractant,tumor necrosis factor-αand monocyte chemoattractant protein-1 could be decreased in the three dosage groups of PDL(P<0.01).PDL treatment not only lowered the mortality but also extended the survival duration in mice infected with MDR-PA.It was found after sub-MIC concentration of levofloxacin induced resistance of Pseudomonas aeruginosa to pneumonia in mice.Compared with the model group,the lung index of mice in high and medium PDL doses was significantly reduced(P<0.05),with inhibition rates of 32.16%and 37.73%,respectively.Conclusion:PDL demonstrates protective effects against MDR-PA infection pneumonia,notably decreasing serum inflammatory factor levels.It shows promise in mitigating antibiotic resistance and offers potential for treating pneumonia resulting from Pseudomonas aeruginosa resistance.

Discussion on the Chinese Materia Medica Under EU Regulations for Traditional Herbal Medicines

Traditional Chinese medicine(TCM)is a valuable resource for the Chinese nation.With its rich theoretical foundation and long-term practical experience,it provides a solid foundation and rich source for various types of pharmaceutical innovation.The European Union(EU)established Committee on Herbal Medicinal Products(HMPC)and issued 2004/24/EC Directive and 2001/83/EC Directive,which provides legal protection for strengthening the management of traditional medicines and unifying the drug registration standards of member states.It also provides the possibility for Chinese herbal medicine,a precious medical resource,to enter the European market and benefit European citizens.However,in the application process by Chinese traditional medicine manufacturers,there are practical problems such as unclear mechanism of action and differences in drug quality requirements between China and EU.By selecting an appropriate application direction and strategy,the type of drug applied is inclined to the direction of simpler drugs with a simpler mechanism of action.Meanwhile,the policy advantages of local drug manufacturers should be fully taken to strengthen bilateral or multilateral cooperation and other ways to deal with it,providing the possibility to promote the traditional Chinese herbal medicine to go abroad,better serve the people of all countries,and promote the international development of TCM.

Seasonal variations in the plant diet of the Chinese Monal revealed by fecal DNA metabarcoding analysis

The Chinese Monal(Lophophorus thuysii)is an alpine-obligate galliform species of global conservation priority.It has been listed as a first class protected wildlife species in China,requiring conservation actions during the 14 th Five-Year Plan period.However,the diet composition of Chinese Monal and its seasonal variations have rarely been studied,constraining the effective conservation of the species.Here,we investigated the plant diet composition of the Chinese Monal and its seasonal variations using a DNA metabarcoding approach on fecal samples.We collected 190 fecal samples of the Chinese Monals from the central Qionglai Mountains located in China,and analyzed the plant diet of this species using a DNA metabarcoding approach.Taxonomic profiling of higher plants in the fecal samples was performed using the second internal transcribed spacer(ITS2)amplicon.Downstream analyses,including rarefaction curves,nonmetric multidimensional scaling(NMDS)and permutational multivariate analysis of variance(PERMANOVA),were used to explore the seasonal variations in diet composition.The Chinese Monal foraged a wide range of plant recipes composed of 35 families and 83 genera throughout the year,with Brassicaceae,Apiaceae,and Poaceae as the dominant families,and Cardamine as the dominant genus.The species consumed plants from 62 genera from 28 families during the breeding season(n=81)and 66 genera from 31 families during the non-breeding season(n=109).Further,the plant diet composition significantly varied between the breeding and non-breeding seasons,especially for the frequency of occurrence and relative read abundances at genus level.Our study analyzed the plant diet of the Chinese Monal at a high resolution for the first time,and the results revealed that the seasonal variations in its plant diet composition was adapted to plant phenology and foraging strategy.Fritillaria species,a previously confirmed important food resource for the Chinese Monal,were not detected in any fecal samples,potentially due to overharvesting of Fritillaria bulbs for Traditional Chinese Medicine.Therefore,we highly recommend further restriction of herb gathering in Chinese Monal habitats to facilitate the conservation of this endangered species.Altogether,our study enriches essential ecological information for the Chinese Monal and also provides insights into conservation management for this endangered species.

Dynamic analysis of 10 components of the Chinese herbal compound Wuzhuyu-tang absorbed into rat plasma

To clarify the active components of Wuzhuyu-tang, this study analyzed dynamic changes of 10 ingredients of Wuzhuyu-tang in plasma using combination high performance liquid chromatography-mass spectrometry after oral administration in rats. The results showed that seven ingredients were detected in portal vein plasma after oral administration of 16.3 or 8.15 g/kg equivalent of raw material of Wuzhuyu-tang extract. The absorption rate of limonin, evodiamine, gingerol （6-Gi）, and ginsenoside-Rg1 was greater than that of isorhamnetin-3-O-β-D-glucosyl （6″→1″′）-α-L-rhamnoside, ginsenoside-Rb1 （Rb1）, and ginsenoside-Re （Re）. The time most elements were absorbed into the blood was 30 to 60 minutes after administration. Re, 6-Gi and Rb1 were metabolized faster. The results suggest that the seven ingredients described above are the active components for treating migraines.

Functional characterization and key residues engineering of a regiopromiscuity O-methyltransferase involved in benzylisoquinoline alkaloid biosynthesis in Nelumbo nucifera

Lotus(Nelumbo nucifera),an ancient aquatic plant,possesses a unique pharmacological activity that is primarily contributed by benzylisoquinoline alkaloids(BIAs).However,only few genes and enzymes involved in BIA biosynthesis in N.nucifera have been isolated and characterized.In the present study we identified the regiopromiscuity of an O-methyltransferase,designated NnOMT6,isolated from N.nucifera;NnOMT6 was found to catalyze the methylation of monobenzylisoquinoline 6-O/7-O,aporphine skeleton 6-O,phenylpropanoid 3-O,and protoberberine 2-O.We further probed the key residues affecting NnOMT6 activity via molecular docking and molecular dynamics simulation.Verification using site-directed mutagenesis revealed that residues D316,N130,L135,N176A,D269,and E328 were critical for BIA O-methyltransferase activities;furthermore,N323A,a mutant of NnOMT6,demonstrated a substantial increase in catalytic efficiency for BIAs and a broader acceptor scope compared with wild-type NnOMT6.To the best of our knowledge,this is the first study to report the O-methyltransferase activity of an aporphine skeleton without benzyl moiety substitutions in N.nucifera.The study findings provide biocatalysts for the semisynthesis of related medical compounds and give insights into protein engineering to strengthen O-methyltransferase activity in plants.

Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice

Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.Methods: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.Results: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition,other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interactionmediated cellular communication in promoting liver fibrosis.Conclusions: TCS modulates the cellular activities and fates of several specific cell types(including hepatocytes, HSCs,endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis.Overall, we provide the first comprehensive single-cell atlas of mice livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.

A single-cell landscape of triptolide-associated testicular toxicity in mice

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and downregulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

THE PRESENT SITUATION AND PROSPECTS OF RESEARCHES ON THE PHARMACOLOGY OF COMPOUNDED CHINESE DRUGS

The human body is an organic whole,andtherefore disease in one internal organ often af-fects others.Compounded Chinese herbal drugsare designed as required for the treatment ofvarious diseases according to principles of drugcombination under the guidance of the concep-tion of the integral human body,so a compositeprescription is also an integral whole,and the inte-grity of the compound is aimed at the

Progress and prediction of multicomponent quantification in complex systems with practical LC-UV methods

Complex systems exist widely,including medicines from natural products,functional foods,and biological samples.The biological activity of complex systems is often the result of the synergistic effect of multiple components.In the quality evaluation of complex samples,multicomponent quantitative analysis(MCQA)is usually needed.To overcome the difficulty in obtaining standard products,scholars have proposed achieving MCQA through the“single standard to determine multiple components(SSDMC)”approach.This method has been used in the determination of multicomponent content in natural source drugs and the analysis of impurities in chemical drugs and has been included in the Chinese Pharmacopoeia.Depending on a convenient(ultra)high-performance liquid chromatography method,how can the repeatability and robustness of the MCQA method be improved?How can the chromatography conditions be optimized to improve the number of quantitative components?How can computer software technology be introduced to improve the efficiency of multicomponent analysis(MCA)?These are the key problems that remain to be solved in practical MCQA.First,this review article summarizes the calculation methods of relative correction factors in the SSDMC approach in the past five years,as well as the method robustness and accuracy evaluation.Second,it also summarizes methods to improve peak capacity and quantitative accuracy in MCA,including column selection and twodimensional chromatographic analysis technology.Finally,computer software technologies for predicting chromatographic conditions and analytical parameters are introduced,which provides an idea for intelligent method development in MCA.This paper aims to provide methodological ideas for the improvement of complex system analysis,especially MCQA.