[Natural 5α-reductase inhibitors in treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia(BPH) is a common disease of the male urinary system, and its incidence rate in China is increasing. However, the mechanism underlying the pathogenesis of BPH remains unclear. Some studies demonstrated that the incidence of BPH was related to the change in the levels of steroid hormones. Too high content of dihydrotestosterone(DHT) in the body may cause BPH and other related diseases. Testosterone(T) is converted to DHT by 5α-reductase(SRD5A). By inhibiting the activity of this enzyme, the production of DHT can be reduced, and then the incidence of BPH can be lowered. Therefore, it has drawn great attention to screen and discover safer and more effective 5α-reductase inhibitors from natural medicines to treat prostatic hyperplasia without affecting the physiological function of men. This review summarizes the characteristics and tissue distribution of 5α-reductase, the discovery of 5α-reductase inhibitors in traditional Chinese medicine and natural medicines, 5α-reductase inhibitors commonly used in clinical practice and their side effects, as well as the animal models of prostatic hyperplasia and common detection indicators, aiming to provide a reference for more in-depth understanding and research about BPH and development of drugs.

Uncovering the secrets of agarwood aroma according to regions and grades using a comprehensive analytical strategy.

Agarwood holds significant importance as a valuable resource for aromatic purposes, however, key components responsible for aroma and the differences between regions and grades remain to be deeply elucidated. Thus, the odors of agarwood sourced from typical zones, as well as the renowned Kynam agarwood, were analyzed by HS-SPME Arrow GC-MS in SCAN and MRM modes. The integrated strategy proposed herein exploits the respective advantages of non-targeted and targeted analysis. In addition to a total of 55 volatile components identified from the NIST database, 114 odor components were matched according to the Smart Aroma Database, and a series of differential compounds was also unearthed and quantified.

Comprehensive profiling of amino acids and derivatives in biological samples: A robust UHPLC-MS/MS method for investigating acute lung injury.

The severe respiratory dysfunctions associated with acute lung injury (ALI) and its sequelae have a high morbidity and mortality rate, are multifactorial, and lack a viable treatment. Considering the critical function that amino acids and derivatives play in the genesis of illnesses and the regulation of metabolic processes, monitoring the levels of metabolites associated with amino acids in biological matrices is necessary and interesting to study their pathological mechanisms. Exploring the dynamics of amino acids and derivatives level and searching for biomarkers provides improved clinical ideas for the diagnosis and treatment of ALI. Therefore, we developed an ultra-high-performance liquid chromatography-electrospray tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously determine the amino acid and derivatives metabolic levels to study amino acid profiles in different biological samples to facilitate clinical research of ALI. In this study, 48 amino acids and derivatives, including neurotransmitters, polyamines, purines, and other types, were quantified simultaneously in a fast, high-throughput, sensitive, and reliable manner within a 15-minute run time without derivatization. No relevant studies have been reported to quantify these 48 amino acid metabolites in three biological samples simultaneously. Satisfactory linearity (R > 0.995), inter-day and intra-day accuracy (85.17-112.67 % and 85.29-111.60 %, respectively), inter-day and intra-day precision (RSD < 13.80 % and RSD < 12.01 %, respectively), matrix effects (81.00 %-118.00 %), recovery (85.09 %-114.65 %) and stability (RSD < 14.72 %) were all demonstrated by the optimized method's successful validation for all analytes. In addition, the suggested method was effectively implemented in plasma, urine, and lung tissue from normal mice and mice with ALI, with the aim of finding potential biomarkers associated with ALI. Potential biomarkers were screened through multivariate statistical analysis and volcanic map analysis, and the changes of markers in ALI were again identified through heat map analysis and correlation analysis with biochemical indicators, which provided ideas and references for subsequent mechanism studies. Here, the technique created in this work offers a quick and dependable way to perform an integrated analysis of amino acids in a variety of biological materials, which can provide research ideas for understanding the physiopathological state of various diseases.

Mass spectrometric analysis strategies for pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) in food and natural preparations have received widespread attention due to their hepatotoxicity, genotoxicity, and embryotoxicity. Mass spectrometry (MS), as a high resolution, high sensitive, and high throughput detection tool, has been the most commonly used technique for the determination of PAs. The continuous advancement of new technologies, methods, and strategies in the field of MS has contributed to the improvement of the analytical efficiency and methodological enhancement of PAs. This paper provides an overview of the structure, toxicity properties and commonly employed analytical methods, focusing on the concepts, advances, and novel techniques and applications of MS-based methods for the analysis of PAs. Additionally, the remaining challenges, future perspectives, and trends for PA detection are discussed. This review provides a reference for toxicological studies of PAs, content monitoring, and the establishment of quality control and safety standards for herbal and food products.

Rare ginsenosides: A unique perspective of ginseng research.

BACKGROUND: Rare ginsenosides (Rg3, Rh2, C-K, etc.) refer to a group of dammarane triterpenoids that exist in low natural abundance, mostly produced by deglycosylation or side chain modification via physicochemical processing or metabolic transformation in gut, and last but not least, exhibited potent biological activity comparing to the primary ginsenosides, which lead to a high concern in both the research and development of ginseng and ginsenoside-related nutraceutical and natural products. Nevertheless, a comprehensive review on these promising compounds is not available yet. AIM OF REVIEW: In this review, recent advances of Rare ginsenosides (RGs) were summarized dealing with the structurally diverse characteristics, traditional usage, drug discovery situation, clinical application, pharmacological effects and the underlying mechanisms, structure-activity relationship, toxicity, the stereochemistry properties, and production strategies. KEY SCIENTIFIC CONCEPTS OF REVIEW: A total of 144 RGs with diverse skeletons and bioactivities were isolated from Panax species. RGs acted as natural ligands on some specific receptors, such as bile acid receptors, steroid hormone receptors, and adenosine diphosphate (ADP) receptors. The RGs showed promising bioactivities including immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes, and interaction with gut microbiota. Clinical trials indicated the potential of RGs, while high quality data remains inadequate, and no obvious side effects was found. The stereochemistry properties induced by deglycosylation at C (20) were also addressed including pharmacodynamics behaviors, together with the state-of-art analytical strategies for the identification of saponin stereoisomers. Finally, the batch preparation of targeted RGs by designated strategies including heating or acid/ alkaline-assisted processes, and enzymatic biotransformation and biosynthesis were discussed. Hopefully, the present review can provide more clues for the extensive understanding and future in-depth research and development of RGs, originated from the worldwide well recognized ginseng plants.

A comprehensive profiling of renin-angiotensin system in mouse and human plasma by a rapid quantitative analysis of 14 angiotensin peptides using ultrahigh-performance liquid chromatography with tandem mass spectrometry.

BACKGROUND: The renin-angiotensin system produces a series of biologically active angiotensin (Ang) peptides. These Ang peptides are the major regulators of blood pressure and Na homeostasis, and play a critical role in maintaining cardiovascular and fluid homeostasis. The concentration of Ang peptides in the body is at trace levels, making their detection and quantification a challenge. In this study, a rapid and sensitive analytical method using mass spectrometry coupled with ultrahigh-performance liquid chromatography (UHPLC/MS) was developed to simultaneously quantify 14 Ang peptides. METHODS: UHPLC/MS was employed to quantify 14 Ang peptides in mouse and human plasma. An HSS T3 column (2.1 × 100 mm, 1.8 µm) with an HSS T3 precolumn and triple-quadrupole mass spectrometer combined with an electrospray ionization source were utilized. Sample pretreatment involved a one-step protein precipitation using methanol. The total analysis time was within 7.5 min and the target peptides were detected in positive ion mode and quantified by selected reaction monitoring mode. RESULTS: The method was validated for linearity, detection and quantification limits, precision, stability, recovery and matrix effect. The limits of detection of Ang II, Ang III, Ang-(1-7), Ang-(2-7), Ang-(3-7), Ang-(1-9), bradykinin, Asn1 and Val5 -Ang II are all less than 1 pg mL-1 , indicating high sensitivity. The intra-day and inter-day precision was within 15%, and the accuracy was between 85% and 115%. Meanwhile, the sample and reference solution were stable within 48 h, and the recovery and matrix effect met the quantitative requirements. CONCLUSIONS: The method is currently reported to allow the largest number of Ang peptide species to be detected at one time. In addition, the proposed method offers a fast and reliable approach for comprehensive analysis of Ang metabolism in biological samples, facilitating research on the physiological and pathological states of cardiovascular, kidney and respiratory diseases.

Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples.

Bile acids (BAs) are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps (CGP) and cholesterol gallstones (CGS). To date, there is neither systematic study on BAs profile of CGP or CGS, nor the relationship between them. To explore the metabolomics profile of plasma BAs in healthy volunteers, CGP and CGS patients, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma. The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples. The results show that, compared to healthy volunteers, CGP and CGS were both characterized by the significant decrease in plasma BAs pool size, furthermore CGP and CGS shared aberrant BAs metabolic characteristics. Chenodeoxycholic acid, glycochenodeoxycholic acid, λ-muricholic acid, deoxycholic acid, and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases. Subsequent analysis showed that clinical characteristics including cysteine, ornithine and body mass index might be closely related to metabolisms of certain BA modules. This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Red ginseng extracts ameliorate high-fat diet-induced obesity and insulin resistance by activating the intestinal TGR5-mediated bile acids signaling pathway.

BACKGROUND: Obesity has emerged as a worldwide metabolic disease, given its rapid growth in global prevalence. Red ginseng extracts (RGS), one of the traditional processed products of ginseng, show the potential to improve the metabolic phenotype of obesity. However, the RGS mechanism for regulating obesity and late insulin resistance remains to be clarified. PURPOSE: This study aimed to emphasize the potential use of RGS in treatment of obesity and insulin resistance (IR) and explore the underlying mechanism affecting glucose and lipid metabolism improvements. METHODS: The role of RGS was evaluated in a high-fat diet (HFD) rodent model. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to characterize the glucose metabolism level. The expression of lipolysis proteins and uncoupling protein-1 (UCP-1) were investigated by western blot. Glucagon-like peptide-1 (GLP-1) and apical sodium-dependent bile acid transporter (ASBT) protein expression in the intestine were determined via immunofluorescence. UPLC-Q-TOF-MS were used to detect the alterations in bile acids (BAs) levels in serum, ileum, and inguinal white adipose tissue (iWAT). In addition, intestine-specific Tgr5 knockout mice were employed to verify the efficacy of RGS in improving obesity. RESULTS: RGS treatment alleviated dietary-induced dyslipidemia and IR in obese mice in a dose-dependent manner and improved glucose and insulin tolerance, and energy expenditure. RGS treatment significantly reduced lipid deposition and induced GLP-1 secretion in the intestine of wild-type mice but not in Tgr5ΔIN obese mice. Furthermore, RGS intervention increased BA levels in serum, ileum, and iWAT. The increase of circulating BAs in mice was related to the activation of ileal TGR5 and the promotion of ASBT translocation to the plasma membrane, thus affecting BA transport. Next, the increased level of circulating BAs entered the periphery, which might facilitate lipolysis and energy consumption by activating TGR5 in iWAT. CONCLUSION: Our results demonstrated that RGS significantly alleviated HFD-induced obesity and insulin resistance in mice. RGS intervention improved glucose metabolism, promoted lipolysis, and energy metabolism by activating TGR5 in the intestine. In addition, we found that activating intestinal TGR5 facilitated the localization of ASBT to the plasma membrane, which ultimately promoted the transport of BAs to regulate metabolic phenotype.

Identification and validation of diagnostic biomarkers of coronary artery disease progression in type 1 diabetes via integrated computational and bioinformatics strategies.

OBJECTIVE: Our study aimed to identify early peripheral blood diagnostic biomarkers and elucidate the immune mechanisms of coronary artery disease (CAD) progression in patients with type 1 diabetes mellitus (T1DM). METHODS: Three transcriptome datasets were retrieved from the Gene Expression Omnibus (GEO) database. Gene modules associated with T1DM were selected with weighted gene co-expression network analysis. Differentially expressed genes (DEGs) between CAD and acute myocardial infarction (AMI) peripheral blood tissues were identified using limma. Candidate biomarkers were selected with functional enrichment analysis, node gene selection from a constructed protein-protein interaction (PPI) network, and 3 machine learning algorithms. Candidate expression was compared, and the receiver operating characteristic curve (ROC) and nomogram were constructed. Immune cell infiltration was assessed with the CIBERSORT algorithm. RESULTS: A total of 1283 genes comprising 2 modules were detected as the most associated with T1DM. In addition, 451 DEGs related to CAD progression were identified. Among them, 182 were common to both diseases and mainly enriched in immune and inflammatory response regulation. The PPI network yielded 30 top node genes, and 6 were selected using the 3 machine learning algorithms. Upon validation, 4 genes (TLR2, CLEC4D, IL1R2, and NLRC4) were recognized as diagnostic biomarkers with the area under the curve (AUC) > 0.7. All 4 genes were positively correlated with neutrophils in patients with AMI. CONCLUSION: We identified 4 peripheral blood biomarkers and provided a nomogram for early diagnosing CAD progression to AMI in patients with T1DM. The biomarkers were positively associated with neutrophils, indicating potential therapeutic targets.

TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner.

Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site "A" to "T", and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI.

Study on herb-herb interaction between active components of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma based on transporters using UHPLC-MS/MS.

The combined efficacy in lowering serum lipid levels and increasing kidney protection of Plantago asiatica L. seed (Plantago) and Coptis chinensis Franch. rhizoma (Coptis) is far better than the effects of either herb alone. This finding suggests that there must be some degree of herb-herb interactions (HHI) affect potency. Here, we chose geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA) as active components in Plantago, and berberine (BBR) as the active component in Coptis, and, using transporter gene-transfected Madin-Darby canine kidney (MDCK) cells in combination with specific substrates and inhibitors, investigated Plantago- Coptis HHIs. We also established a UPLC-MS/MS analytical method to determine substrate content. Results showed that PLA in Plantago was a substrate of rOCT1/2 and rMATE1, and had inhibitory effects on rOCT2 and rMATE1. We also found that ACT is a substrate of rMATE1, but GPA was not a substrate of any transporter that we investigated. When BBR was used as the substrate, the inhibition rate of 10 µM PLA was 53.6% on rOCT2 and 31.5% on rMATE1. The inhibition rates of 30 µM ACT and 30 µM GPA on rMATE1 were 47.0% and 31.0%, respectively. Thus, our findings suggest that GPA, ACT, PLA, and BBR have competitive interactions that are driven by the rOCT2 and rMATE1 transporters. These interactions affect the transport and excretion of compounds and result in efficacy changes after co-administration.

The history, stereochemistry, ethnopharmacology and quality assessment of borneol.

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol (BO) represents a global trade-driven spreading of ethnic medicine traceable to the classical age, and won its name specific to its original habitat "Borneo". BO shows broad spectral pharmacological effects, such as anti-inflammatory, analgesic, antipyretic, inducing resuscitation, and widely applied in the protection and treatment of cardiovascular and cerebrovascular diseases, used singly or mostly in compound formulae. AIM OF THE STUDY: Three stereoscopic configuration forms of BO, l-borneol (LB), d-borneol (DB), and dl-borneol (synthetic, SB), are formulated in broad spectral application, yet their diverse pharmacodynamic and pharmacokinetic properties caused by configurations, and accurate assay and quality assessment are often overlooked. A systematic review and analysis of lumped studies and applications is necessary to clarify the relationship between configuration and its original plant, analysis method, activity and side effect BO in order to guarantee the efficacy and safety during their application. MATERIALS AND METHODS: The public databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure were referenced to summarize a comprehensive research and application data of BO published up to date. RESULTS: This review includes following sections: History and current status, Stereochemistry, Ethnopharmacology, and Quality assessment. In the section of history, the changes of the plant origins of the two isomeric forms of natural BO were described respectively, and the methods for synthetic racemate SB were also included. The section of stereochemistry deals with the stereoscopic structures, physical/chemical property, optical rotation of the three forms of BO, as well as the main related substances like isoborneol, obtained in SB via chemical transformation of camphor and turpentine oil. In the section of Ethnopharmacology, pharmacological activities and pharmacokinetics of different forms of BO were discussed. BO is usually used as an "adjuvant", by enhancing the permeability of the blood-brain barrier and intervene the ADME/T pathways of the other ingredients in the same formulation. In the section of quality assessment, the analytical methods, including chromatography, especially GC, and spectroscopy were addressed on the chiral separation of the coexisting enantiomers. CONCLUSIONS: This overview systematically summarized three forms of BO in terms of history, stereochemistry, ethnopharmacology, and quality assessment, which, hopefully, can provide valuable information and strategy for more reasonable application and development of the globally reputed ethnic medicine borneol with characteristics in stereochemistry.

Advances in mass spectrometry imaging for toxicological analysis and safety evaluation of pharmaceuticals.

Safety issues caused by pharmaceuticals have frequently occurred worldwide, posing a tremendous threat to human health. As an essential part of drug development, the toxicological analysis and safety evaluation is of great significance. In addition, the risk of pharmaceuticals accumulation in the environment and the monitoring of the toxicity from natural medicines have also received ongoing concerns. Due to a lack of spatial distribution information provided by common analytical methods, analyses that provide spatial dimensions could serve as complementary safety evaluation methods for better prediction and evaluation of drug toxicity. With advances in technical solutions and software algorithms, mass spectrometry imaging (MSI) has received increasing attention as a popular analytical tool that enables the simultaneous implementation of qualitative, quantitative, and localization without complex sample pretreatment and labeling steps. In recent years, MSI has become more attractive, powerful, and sensitive and has been applied in several scientific fields that can meet the safety assessment requirements. This review aims to cover a detailed summary of the various MSI technologies utilized in the biomedical and pharmaceutical area, including technical principles, advantages, current status, and future trends. Representative applications and developments in the safety-related issues of different pharmaceuticals and natural medicines are also described to provide a reference for pharmaceutical research, improve rational clinical medicine use, and ensure public safety.

A complementary chromatographic strategy for integrated components characterization of Imperatae Rhizoma based on convergence and liquid chromatography combined with mass spectrometry and molecular network.

The complexity of natural ingredients and the diversity of preparations are the major obstacles to the quality evaluation of traditional Chinese medicines (TCMs). A more comprehensive characterization of herbal compounds using different types of chromatographic separation techniques and covering a diverse polarity range can help evaluate the quality of TCMs. In this study, we first proposed a comprehensive method for characterizing compounds derived from Imperatae Rhizoma by combining the complementary strengths of UPCC-QTOF-MS (ultra-performance convergence chromatography coupled with quadrupole-time of flight mass spectrometry) with UPLC-QTOF-MS (ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry). The method based on the UNIFI scientific platform significantly shortened the analysis time and enabled a more comprehensive characterization of known and unreported compounds. Meanwhile, a feature-based molecular network (FBMN) was established on the Global Natural Product Social (GNPS) to infer potential compounds by rapidly classifying and visualizing these components. A total of 62 compounds in Imperatae Rhizoma were jointly characterizedand classified into six types. In comparison, the UPCC-QTOF-MS technology individually characterized 17 components, including lactones, phenols, aldehydes, phenylpropanoids, and small polar organic acids. The UPLC-QTOF-MS technology characterized 16 compounds mainly phenylpropionic acids, flavonoid glycosides, and chromone glycosides. Furthermore, three types of characteristic compounds could be well aggregated into an FBMN approach. Five possible potential new compounds were detected through the supplementary identification of GNPS and the correlation analysis of vicinal known compounds. The strategy was first applied to Imperatae Rhizoma and facilitated the characterization of a large quantity of data to provide comprehensive chemical composition results. This approach can be easily extended to the study of the material basis of other herbs or preparations in order to improve the accuracy of herb quality evaluation.

Development of Green and Efficient Extraction of Bioactive Ginsenosides from Panax ginseng with Deep Eutectic Solvents.

The extraction of active constituents from natural sources in a green and efficient manner is considered an important field in the pharmaceutical industry. In recent years, deep eutectic solvents (DESs), a new type of green solvent, have attracted increasing attention. Therefore, we aimed to establish a green and high-efficiency extraction method for ginsenosides based on DESs. This study takes Panax ginseng as a model sample. Eighteen different DESs were produced to extract polar ginsenosides. Ultrasound-assisted extraction (UAE) was applied for simplicity and efficiency. A binary DES synthesized using choline chloride and urea at a proportion of 1:2 prepared by a heating stirring method is proven to be more effective than other solvents, such as the widely used 70% ethanol for the extraction of ginsenosides. Three variables that might affect the extraction, including the DES content in the extraction solvent, liquid/solid ratio, and ultrasound extraction time, were evaluated for optimization. The optimum extraction conditions for ginsenosides were determined as follows: DES water content of 20 wt%, liquid/solid ratio of 15 mL g-1, and an ultrasonic extraction time of 15 min. The extraction yield for the optimized method is found to be 31% higher than that for 70% ethanol, which achieves efficient extraction. This study shows that DESs are available to extract ginsenosides for use in traditional Chinese medicine. The discovery also contributes to further research into the green extraction of ginsenosides.

Rapid analysis of differential chemical compositions of Poria cocos using thin-layer chromatography spray ionization-mass spectrometry.

Poria cocos, with medicinal and edible properties, contains multiple chemical components that pose difficulties in its quality control. Herein, we established a simple thin-layer chromatography spray ionization-mass spectrometry (TLCSI-MS) device that allows the simultaneous separation and identification of bioactive compounds. The triterpene acids in different medicinal parts of Poria cocos were characterized, and the markers of differences were revealed. The quantitative analysis of its pharmaceutical preparation has also been performed to verify the feasibility. The study provides a new analytical perspective for the screening and identification of multiple compounds and a good option for the quality evaluation of herbal medicines and foods.

Mass spectrometry-based profiling and imaging strategy, a fit-for-purpose tool for unveiling the transformations of ginsenosides in Panax notoginseng during processing.

BACKGROUND: Panax notoginseng, a valuable medicinal plant, is traditionally used to treat trauma, body pain, and cardiovascular diseases in two clinical forms including raw (crude) and processed form. Processing-triggered compound transformation is responsible for the distinct bioactivity between raw and processed Panax notoginseng. Nevertheless, investigating the chemical diversity and dynamic transformation pattern of processed Panax notoginseng is challenging. METHODS: A new approach, which integrates multi-components characterization, processing trajectory depiction, discovery of differential markers, transformation mechanism of metabolites, in situ spatial distribution and transformation of metabolites, was established to elucidate the role of processing on the holistic chemical transformations of Panax notoginseng (PN). RESULTS: In this study, 136 ginsenosides (mainly rare ginsenosides) were identified or tentatively characterized and the temperature-dependent chemical variation trajectory was depicted via principal component analysis (PCA). Nineteen processing-associated markers were confirmed by orthogonal partial least squares-discriminant analysis (OPLS-DA). For the first time, the transformation pathway of ginsenosides during processing were elucidated by integrating the precursor ion scan (PIS) and mimic processing strategy that involves with deglycosylation, dehydration, hydration, acetylation, and isomerization. Results of mass spectrometry imaging (MSI) revealed the major ginsenosides M-Rb1, R1, Rg1, Rb1, Rd, and Re exhibited distinct spatial distribution pattern that are highly abundant in the xylem and showed a downward trend during processing. We firstly depicted the spatial distribution of processing-triggered rare ginsenosides (Rg3, Rk1, Rg5, etc.), and in situ transformation of ginsenosides was discovered in the process of steaming. Additionally, this variation trend was consistent with untargeted metabolomics results. CONCLUSION: This study comprehensively revealed chemical diversity and dynamic transformation pattern and depicted the spatial distribution of ginsenosides of PN during processing. It could provide a clue for the distinct bioactivities between raw and processed PN and elucidate the role of processing on the holistic chemical transformations of natural products, more importantly, the proposed strategy is valuable for the quality evaluation and control of the processing of natural product.

[Research advances of chemical constituents and analytical methods of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium].

Citri Reticulatae Pericarpium Viride(CRPV) and Citri Reticulatae Pericarpium(CRP) are two commonly used Chinese medicinal materials. They have the same origin while are harvested in different seasons and have different clinical effects. They contain similar chemical components, like flavonoids, terpenes, volatile oils, and alkaloids. Although it has been demonstrated that differential components exist between them, there is still a lack of systematic comparison. Many studies have reported the chemical composition and quality evaluation of CRPV and CRP, including the characterization of flavonoids, alkaloids, and volatile oils via thin-layer chromatography, high-performance liquid chromatography, gas chromatography, infrared spectroscopy, and ultraviolet spectroscopy. A few studies have explored the differences between CRPV and CRP. In this paper, we systematically summarized the reported chemical composition, analytical methods, and quality evaluation of CRPV and CRP in recent ten years, aiming to facilitate the research on the pharmacodynamic material basis, quality evaluation, and standard improvement of CRPV and CRP.