Ingredients Of Traditional Chinese Medicine Research Articles

Wave type fiber SPR sensor for rapid and highly sensitive detection of hyperoside

The fiber surface plasmon resonance (SPR) sensor used for the detection of active ingredients in traditional Chinese medicine has the problems of low sensitivity and difficult specific recognition. This paper proposed a wave type fiber SPR sensor, which reduced the mode of transmitted light through a periodic wave structure and caused concentrated and total reflection of the transmitted beam at the interface between the bent peak cladding and the air. A 50 nm gold film was coated on the surface of the cladding in the wave structure area to form the SPR sensing area. By controlling the width and height of the wave structure to control the total reflection angle of the transmitted light, i.e., the SPR incidence angle, the sensitivity of the fiber SPR sensor was effectively improved to 4972 nm/RIU. Furthermore, HSP90AA protein was modified on the gold film of the sensor to achieve specific detection of hyperoside. The longest single detection time was only 3 minutes, and the detection sensitivity was 0.53 nm/(µg/ml), with a detection limit as low as 0.68µg/ml, which is comparable to liquid chromatography. The proposed wave type fiber SPR sensor is fast in production and has high structural mechanical strength, providing a new approach for the rapid, highly sensitive, and specific detection of active ingredients in traditional Chinese medicine.

Preparation and chromatographic evaluation of 9-oxa-10-phosphophenanthrene 10-oxide bonded phenyl stationary phase and investigation of its retention mechanism through nuclear magnetic resonance spectroscopy

BackgroundIn reversed-phase liquid chromatography, the C18 alkyl bonded phase, as the primary stationary phase, is widely used in pharmaceutical and food analysis. The phenyl bonded phase often serves as a complementary choice to the C18 phase to enhance the separation performance of specific categories of compounds. However, both C18 and the currently available phenyl bonded phase chromatography columns show room for further optimization in improving the separation efficiency of specific compound classes, such as dihydroflavonoids. Additionally, the potential role and impact of introducing phosphorus groups into chromatographic stationary phases have not been fully explored, indicating a promising direction for research. ResultsIn the present work, we prepared a novel phenyl stationary phase by bonding 9-oxa-10-phosphaphenanthrene 10-oxide onto silica gel. The obtained material was characterized by scanning electron microscopy, fourier transforms infrared spectroscopy, and elemental analysis. The results show that 9-oxa-10-phosphaphenanthrene 10-oxide was successfully bonded on the silica surface with a load of 3.90 %. Further chromatographic characterization in high-performance liquid chromatography exhibited high column efficiency (40,792 plates m-1 for the determination of biphenyl) and good stability (RSD of 0.28 %∼5.38 %). Moreover, we made a detailed study of the column separation mechanism by nuclear magnetic resonance spectroscopy titration experiment. Comparing to commercial phenyl column, the proposed stationary phase showed shorter retention time and higher throughput. In addition, the stationary phase has a strong ability to separate multiple types of compounds, which provides a new strategy for the separation of complex samples, such as active ingredients in traditional Chinese medicine. SignificanceWe have developed a novel phenyl column and conducted a comprehensive examination of its chromatographic performance, demonstrating excellent separation capabilities and high efficiency for both nonpolar and moderately polar aromatic compounds. Additionally, we explored the impact of phosphorus-containing groups on the separation performance of chromatographic stationary phases.

UHPLC-PDA-Q-TOF-MS-α-amylase-FLD activity detection system and molecular docking.

Traditional and some scientific literature document the antidiabetic effects of the Ziziphi Spinosae Semen (ZSS). However, the bioactive compounds of ZSS responsible for the antidiabetic effects are not well known. This study aimed to investigate the material basis of the antidiabetic effects of ZSS by inhibiting α-amylase. An online analysis platform was established and optimized using an ultra-performance liquid chromatography-photo-diode array-quadrupole-time-of-flight-mass spectrometry-α-amylase-fluorescence detector (UHPLC-PDA-Q-TOF-MS-α-amylase-FLD) system to screen α-amylase inhibitors in ZSS rapidly. The inhibitory effect of these compounds was confirmed by molecular docking screening. and the molecular interactions between α-amylase and active compounds were evaluated, which strongly supported the experimental results. Seventy-eight compounds were identified in the ZSS extract, eleven of which were screened to have significant α-amylase binding activity. This study demonstrated the feasibility of using an established platform to screen for effective components in ZSS, providing a practical method for the rapid screening of potential antidiabetic active ingredients in traditional Chinese medicine.

MM/GB(PB)SA integrated with molecular docking and ADMET approach to inhibit the fat-mass-and-obesity-associated protein using bioactive compounds derived from food plants used in traditional Chinese medicine

IntroductionObesity is currently a major global concern, requiring the development of effective therapeutics. This study determines the inhibitory activity against FTO (fat mass and obesity-associated protein) of food plant-derived bioactive compounds of TCM (traditional Chinese medicine) importance, by in silico approaches. MethodsFood plant-derived phytochemicals, such as curcumin (CCMN), cajaisoflavone (CJIF), cyanidin-3-O-glucoside (C3OG) and pelargonidin-3-glucoside (P3GS), were selected as ligands, and docked to FTO. The reference FTO-inhibitor used was meclofenmic acid (MCFA). MDS (molecular dynamic simulations) was accomplished with 10 ns run for the docked complex of FTO with the most potential phytocompound. The phytochemicals were subjected to bioactivity scoring, Lipinski's rule of five screening, and ADMET prediction. Law ResultsMolecular docking demonstrated binding energies of -9.4, -8.8, -8.7 and -8.2 kcal/mol for CCMN, CJIF, C3OG and P3GS, respectively. The reference inhibitor MCFA had binding energy of -7.8 kcal/mol, and therefore, the FTO inhibition capacity of the ligands were in order of CCMN > C3OG > P3GS > CJIF > MCFA. The FTO residues His231, Ser229, Val228, Leu109, Tyr108 and Pro93 played crucial role in protein-ligands interaction displaying hydrogen bonds and hydrophobic contacts. MDS-based MM/GB(PB)SA binding free energies authenticated CCMN (-6.67/-8.77 kcal/mol) as a stronger FTO inhibitor than MCFA (0.19/-0.02 kcal/mol). Pharmacological properties of the phytochemicals predicted were comparable to MCFA standard. DiscussionTCM compounds of botanical origin are important for the effective management of obesity. In the current study, all the phytochemicals, the potential TCM ingredients, with acceptable pharmacological properties displayed excellent binding affinity and stronger inhibitory activity against FTO, compared to MCFA. FTO_CCMN displayed more energetic stability compared to FTO_MCFA using MM/GB(PB)SA approaches. Overall, this study paved the basis of FTO-associated obesity management with food plant-based therapeutics of TCM importance in the globe.

Exploring the chemical compositions of Fufang Yinhua Jiedu granules based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry combined with multistage intelligent data annotation strategy

Fufang Yinhua Jiedu granules (FYJG) is a Traditional Chinese Medicine (TCM) compound formulae preparation comprising ten herbal drugs, which has been widely used for the treatment of influenza with wind-heat type and upper respiratory tract infections. However, the phytochemical constituents of FYJG have rarely been reported, and its constituent composition still needs to be elucidated. The complexity of the natural ingredients of TCMs and the diversity of preparations are the major obstacles to fully characterizing their constituents. In this study, an innovative and intelligent analysis strategy was built to comprehensively characterize the constituents of FYJG and assign source attribution to all components. Firstly, a simple and highly efficient ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MSE) method was established to analyze the FYJG and ten single herbs. High-accuracy MS/MS data were acquired under two collision energies using high-definition MSE in the negative and positive modes. Secondly, a multistage intelligent data annotation strategy was developed and used to rapidly screen out and identify the compounds of FYJG, which was integrated with various online software and data processing platforms. The in-house chemical library of 2949 compounds was created and operated in the UNIFI software to enable automatic peak annotation of the MSE data. Then, the acquired MS data were processed by MS-DIAL, and a feature-based molecular networking (FBMN) was constructed on the Global Natural Product Social Molecular Networking (GNPS) to infer potential compositions of FYJG by rapidly classifying and visualizing. It was simultaneously using the MZmine software to recognize the source attribution of ingredients. On this basis, the unique chemical categories and characteristics of herbaceous plant species are utilized further to verify the accuracy of the source attribution of multi-components. This comprehensive analysis successfully identified or tentatively characterized 279 compounds in FYJG, including flavonoids, phenolic acids, coumarins, saponins, alkaloids, lignans, and phenylethanoids. Notably, twelve indole alkaloids and four organic acids from Isatidis Folium were characterized in this formula for the first time. This study demonstrates a potential superiority to identify compounds in complex TCM formulas using high-definition MSE and computer software-assisted structural analysis tools, which can obtain high-quality MS/MS spectra, effectively distinguish isomers, and improve the coverage of trace components. This study elucidates the various components and sources of FYJG and provides a theoretical basis for its further clinical development and application.

Degradation-Based Protein Profiling: A Case Study of Celastrol.

Natural products, while valuable for drug discovery, encounter limitations like uncertainty in targets and toxicity. As an important active ingredient in traditional Chinese medicine, celastrol exhibits a wide range of biological activities, yet its mechanism remains unclear. In this study, they introduced an innovative "Degradation-based protein profiling (DBPP)" strategy, which combined PROteolysis TArgeting Chimeras (PROTAC) technology with quantitative proteomics and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques, to identify multiple targets of natural products using a toolbox of degraders. Taking celastrol as an example, they successfully identified its known targets, including inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα), and cellular inhibitor of PP2A (CIP2A), as well as potential new targets such as checkpoint kinase 1 (CHK1), O-GlcNAcase (OGA), and DNA excision repair protein ERCC-6-like (ERCC6L). Furthermore, the first glycosidase degrader is developed in this work. Finally, by employing a mixed PROTAC toolbox in quantitative proteomics, they also achieved multi-target identification of celastrol, significantly reducing costs while improving efficiency. Taken together, they believe that the DBPP strategy can complement existing target identification strategies, thereby facilitating the rapid advancement of the pharmaceutical field.

Chromene-derived red-fluorescent probes for sulfite detection in food and living cells based on an integrated ICT&PET platform

Sulfite, widely used in food and pharmaceutical industries, poses significant health and safety concerns, necessitating efficient detection methods. This study introduces three novel red fluorescent probes (MCC-BT, MCC-TI, and MCC-DM), synthesized by integrating chromene derivatives with various electron-withdrawing groups. These probes effectively detect sulfite in both food samples and living cells, leveraging a mechanism transition from intramolecular charge transfer (ICT) to photo-induced electron transfer (PET). They demonstrate low detection limits (2.0 μM, 0.42 μM, and 0.34 μM, respectively) and offer advantages including large Stokes shifts, minimal interference, and colorimetric capabilities. We also developed smartphone-compatible test paper strips for convenient sulfite detection in real-world samples. The probes' effectiveness is further evidenced through sulfite quantification in Traditional Chinese Medicine ingredients. Additionally, their robust fluorescent imaging potential for cellular sulfite sensing highlights their significant contribution to analytical chemistry and biomedical research.

Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy.

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.

Synthesis and in vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 μM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Spiral cone fiber SPR sensor for detecting ginsenoside Rg1

The conical fiber SPR sensor is easy to manufacture and has been used in biochemical detection research, but it has the problem of structural fragility. This article proposes a spiral cone fiber SPR sensor, which introduces a spiral structure on the 76µm fiber coarse cone, achieving good coupling of the core mode into the cladding mode, and improving the physical strength and practicality of the cone-shaped fiber SPR sensor. By modifying the target protein on the surface of the sensor gold film, specific detection of ginsenoside Rg1, an active ingredient of traditional Chinese medicine ginseng, was achieved. The detection sensitivity was 0.138 nm/(µm/ml) and the detection limit was 0.22µm/ml. The proposed spiral cone fiber SPR sensor provides a new scheme for the specific detection of active ingredients in traditional Chinese medicine, which is structurally stable and physically strong.

A fast and efficient method for screening and evaluation of hypoglycemic ingredients of Traditional Chinese Medicine acting on PTP1B by capillary electrophoresis

As a pivotal enzyme that regulates dephosphorylation in cell activities and participates in the insulin signaling pathway, protein tyrosine phosphatase 1B (PTP1B) is considered to be an important target for the therapy of diabetes. In this work, a rapid and efficient inhibitor screening method of PTP1B was established based on capillary electrophoresis (CE), and used for screening and evaluating the inhibition effect of Traditional Chinese Medicine on PTP1B. Response Surface Methodology was used for optimizing the conditions of analysis. After method validation, the enzyme kinetic study and inhibition test were performed. As a result, the IC50 of PTP1B inhibitors Ⅳ and ⅩⅧ were consistent with reported values measured by a conventional method. It was found that the extracts of Astragalus membranaceus (Fisch) Bunge and Morus alba L. showed prominent inhibition on the activity of PTP1B, which were stronger than the positive controls. Meanwhile, on top of the excellent advantages of CE, the whole analysis time is less than 2 min. Thus, the results demonstrated that a fast and efficient screening method was successfully developed. This method could be a powerful tool for screening inhibitors from complex systems. It can also provide an effective basis for lead compound development in drug discovery.

CDCS-TCM: A framework based on complex network theory to analyze the causality and dynamic correlation of substances in the metabolic process of traditional Chinese medicine

Ethnopharmacological relevanceTraditional Chinese medicine, with the feature of synergistic effects of multi-component, multi-pathway and multi-target, plays an important role in the treatment of cancer, cardiovascular and cerebrovascular diseases, etc. However, chemical components in traditional Chinese medicine are complex and most of the pharmacological mechanisms remain unclear, especially the relationships of chemical components change during the metabolic process. Aim of studyOur aim is to provide a method based on complex network theory to analyze the causality and dynamic correlation of substances in the metabolic process of traditional Chinese medicine. Materials and methodsWe proposed a framework named CDCS-TCM to analyze the causality and dynamic correlation between substances in the metabolic process of traditional Chinese medicine. Our method mainly consists two parts. The first part is to discover the local and global causality by the causality network. The second part is to investigate the dynamic correlations and identify the essential substance by dynamic substance correlation network. ResultsWe developed a CDCS-TCM method to analyze the causality and dynamic correlation of substances. Using the XiangDan Injection for ischemic stroke as an example, we have identified the important substances in the metabolic process including substance pairs with strong causality and the dynamic changes of the core effector substance clusters. ConclusionThe proposed framework will be useful for exploring the correlations of active ingredients in traditional Chinese medicine more effectively and will provide a new perspective for the elucidation of drug action mechanisms and the new drug discovery.

Forsythoside A protects against Zearalenone-induced cell damage in chicken embryonic fibroblasts via mitigation of endoplasmic reticulum stress.

Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin that exerts its toxic effects through various damage mechanisms such as oxidative stress, endoplasmic reticulum stress (ERS), mitochondrial damage, cell cycle arrest, and apoptosis. At present, there are few studies on drugs that can rescue ZEA-induced chicken embryonic fibroblasts damage. Forsythoside A (FA) is one of effective ingredients of traditional Chinese medicine that plays a role in various biological functions, but its antitoxin research has not been investigated so far. In this study, in vitro experiments were carried out. Chicken embryo fibroblast (DF-1) cells was used as the research object to select the appropriate treatment concentration of ZEA and examined reactive oxygen species (ROS), mitochondrial membrane potential, ERS and apoptosis to investigate the effects and mechanisms of FA in alleviating ZEA-induced cytotoxicity in DF-1 cells. Our results showed that ZEA induced ERS and activated the unfolded protein response (UPR) leading to apoptosis, an apoptotic pathway characterized by overproduction of Lactate dehydrogenase (LDH), Caspase-3, and ROS and loss of mitochondrial membrane potential. We also demonstrated that FA help to prevent ERS and attenuated ZEA-induced apoptosis in DF-1 cells by reducing the level of ROS, downregulating GRP78, PERK, ATF4, ATF6, JNK, IRE1, ASK1, CHOP, BAX expression, and up-regulating Bcl-2 expression. Our results provide a basis for an in-depth study of the mechanism of toxic effects of ZEA on chicken cells and the means of detoxification, which has implications for the treatment of relevant avian diseases.

Recent Advances in Biologically Active Ingredients from Natural Drugs for Sepsis Treatment.

Sepsis refers to the dysregulated host response to infection; its incidence and mortality rates are high. It is a worldwide medical problem but there is no specific drug for it. In recent years, clinical and experimental studies have found that many monomer components of traditional Chinese medicine have certain effects on the treatment of sepsis. This paper reviews the advances in research on the active ingredients of traditional Chinese medicine involved in the treatment of sepsis in recent years according to their chemical structure; it could provide ideas and references for further research and development in Chinese materia medica for the treatment of sepsis.

Correlation analysis of secondary metabolites and disease resistance activity of different varieties of Congou black tea based on LC-MS/MS and TCMSP

To investigate the correlation between the difference of secondary metabolites and the disease-resistance activity of different varieties of Congou black tea. Among a total of 657 secondary metabolites identified, 183 metabolites had anti-disease activity, 113 were key active ingredients in traditional Chinese medicine (TCM), 73.22% had multiple anti-disease activities, and all were mainly flavonoids and phenolic acids. The main enriched metabolic pathways were phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, flavonoid biosynthesis, and metabolic pathways. Flavonoid and phenolic acid secondary metabolites were more correlated with anti-disease activity and key active TCM ingredients. Conclusion: The types of JGY and Q601 Congou black tea of the relative contents show large differences in secondary metabolites. Flavonoid and phenolic acid secondary metabolites were identified as the primary factors contributing to the variation in secondary metabolites among different varieties of Congou black tea. These compounds also exhibited a stronger correlation with disease resistance activity.

Determination of 35 prohibited pesticide residues in Saussurea costus by modified QuEChERS method based on multi-walled carbon nanotubes coupled with gas chromatography-tandem mass spectrometry

Saussurea costus, a perennial herb belonging to the Asteraceae family, is a vital ingredient in traditional Chinese medicine. Increased demands for the herb have led to its widespread cultivation in China, but the corresponding increase in pesticide use has raised concerns about pesticide residues. Such residues would affect the safety and global market potential of Saussurea costus. Thus, a simple method is crucial to detect pesticide residues. The QuEChERS technique, in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS), is commonly used for residue detection. However, traditional adsorbents may be unable to purify complex herbal mixtures well, affecting accuracy and instrument performance. Choosing suitable purification materials for Saussurea costus samples with complex matrices is of significant importance. This study focused on the detection of 35 prohibited pesticides in Saussurea costus. A rapid detection method was established by combining the QuEChERS technique with GC-MS/MS and utilizing a combination of multiwalled carbon nanotubes (MWCNTs), octadecylsilane-bonded silica gel (C18), and anhydrous magnesium sulfate (MgSO4) as the purification adsorbent. The samples were extracted with acetonitrile, purified by an improved QuEChERS process, subjected to GC-MS/MS analysis in multiple reaction monitoring (MRM) mode, and quantified using the internal standard method. The purification effects of four materials (C18, MWCNTs, N-propyl ethylenediamine (PSA), and graphitized carbon black (GCB)) and their optimal dosages were investigated by considering the matrix characteristics of the samples. An orthogonal experimental design was employed to optimize the ratio of adsorbent combinations, and the optimal adsorbent combination was determined to be 450 mg of MgSO4, 400 mg of C18, and 50 mg of MWCNTs. Matrix effect (ME) evaluation of the S. costus matrix showed that 31 target compounds strongly exhibited matrix-enhancement effects. Thus, matrix-matched calibration was employed in this study. Methodological investigation revealed that the standard curves for the 35 pesticides exhibited good linearity, with correlation coefficients (r2) greater than 0.9970. The average recoveries at three spiked levels ranged from 69.6% to 126.9%, and the relative standard deviations (RSDs) for parallel groups were all less than 10%. The limits of detection (LODs) and quantification (LOQs) ranged from 0.2 to 5.4 μg/kg and from 0.6 to 18.1 μg/kg, respectively. The developed method was used to screen and detect 35 pesticide residues in 20 batches of S. costus samples, and the target compounds were detected in six batches. The proposed method is simple, sensitive, and accurate. Thus, it is suitable for the rapid screening and detection of the 35 pesticide residues in S. costus and provides technical support for the cultivation, production, and quality control of the herb.

Synthesis and evaluation of bone targeting PLGA nanoparticles loaded with components of traditional Chinese medicine formulas.

Targeted nanoparticles' preparation can enhance local drug concentration and reduce the side effects of drugs in non-targeted organs. At present, many patents have been applied for in the field of bone-targeted nanoparticles' preparations. They play an important role in the treatment and diagnosis of diseases. In this experiment, nanoparticles with bone targeting function were prepared by poly(lactic-co-glycolic acid) (PLGA) copolymer and tetracycline. These nanoparticles contain active ingredients in the Huangqi Sanxian decoction, a kind of Traditional Chinese Medicine (TCM) compound formula. These nanoparticles are predicted to be useful in the treatment of osteoporosis. Synthesis of tetracycline targeting groups was performed by acylation reaction, and PLGA nanoparticles were prepared by the Emulsification-solvent Evaporation Method. The appearance and particle size of the product were evaluated, and the effects of nanoparticles on the physiological activities of osteoblasts were observed. Finally, the bone-targeting ability of targeted nanoparticles in vivo and in vitro was investigated. The average particle size of the nanoparticles was about 200 nm, and the average drug entrapment was 60%. In vitro evaluation of osteoblasts assay showed that the nanoparticles can be well taken by cells. Their good biocompatibility and sustained-release properties reduce the toxic side effects of drugs when they promote osteoblasts' physiological activities. The results of the in vitro and in vivo bone targeting ability assays showed that tetracycline modified nanoparticles could effectively accumulate in the bone, indicating the great bone-targeting ability of the nanoparticles. The use of PLGA to load active components in the TCM compound formulas and remodel targeting groups is expected to improve drug efficacy, reduce drug dosage, and effects on non- action sites. This may provide new ideas for the development of TCM compound dosage forms. In summary, we prepared PLGA nanoparticles of multiple TCM ingredients with bone targeting ability, and they had good morphological appearance, and a promoting effect on various physiological activities of osteoblasts.

Methyl rosmarinate is an allosteric inhibitor of SARS-CoV-2 3 CL protease as a potential candidate against SARS-cov-2 infection

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a new approach by integrating the experimental assay, virtual screening, and the experimental verification, exploring the rapid discovery of active ingredients from TCM prescriptions. To achieve this goal, 4 TCM prescriptions in clinical use for different indications were selected to find the antiviral active ingredients in TCMs. The 3-chymotrypsin-like protease (3CLpro), an important target for fighting COVID-19, was utilized to determine the inhibitory activity of the TCM prescriptions and single herb. It was found that 10 single herbs had better inhibitory activity than other herbs by using a fluorescence resonance energy transfer (FRET) - based enzymatic assay of SARS-CoV-2 3CLpro. The ingredients contained in 10 herbs were thus virtually screened and the predicted active ingredients were experimentally validated. Thus, such a research strategy firstly removed many single herbs with no inhibitory activity against SARS-CoV-2 3CLpro at the very beginning by FRET-based assay, making our subsequent virtual screening more effective. Finally, 4 active components were found to have stronger inhibitory effects on SARS-CoV-2 3CLpro, and their inhibitory mechanism was subsequently investigated. Among of them, methyl rosmarinate as an allosteric inhibitor of SARS-CoV-2 3CLpro was confirmed and its ability to inhibit viral replication was demonstrated by the SARS-CoV-2 replicon system. To validate the binding mode via docking, the mutation experiment, circular dichroism (CD), enzymatic inhibition and surface plasmon resonance (SPR) assay were performed, demonstrating that methyl rosmarinate bound to the allosteric site of SARS-CoV-2 3CLpro. In conclusion, this paper provides the new ideas for the rapid discovery of active ingredients in TCM prescriptions based on a specific target, and methyl rosmarinate has the potential to be developed as an antiviral therapeutic candidate against SARS-CoV-2 infection.

Acetylcholine Analog-Modified Albumin Nanoparticles for the Enhanced and Synchronous Brain Delivery of Saponin Components of Panax Notoginseng.

Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery of active ingredients in traditional Chinese medicine (TCM) poses a significant challenge for modern TCM formulations. Bovine serum albumin (BSA) was modified using 2-methacryloyloxyethyl phosphorylcholine (MPC), an analog of acetylcholine, and subsequently adsorbed the major PNS onto the modified albumin to produce MPC-BSA@PNS nanoparticles (NPs). This novel delivery system facilitated efficient and synchronized transport of PNS across the blood-brain barrier (BBB) through active transport mediated by nicotinic acetylcholine receptors. In vitro experiments demonstrated that the transport rates of R1, Rg1, Rb1, and Rd across the BBB were relatively synchronous in MPC-BSA@PNS NPs compared to those in the PNS solution. Additionally, animal experiments revealed that the brain-targeting efficiencies of R1 + Rg1 + Rb1 in MPC-BSA@PNS NPs were 2.02 and 7.73 times higher than those in BSA@PNS NPs and the free PNS group, respectively. This study presents a simple and feasible approach for achieving the targeted delivery of complex active ingredient clusters in TCM.