Chinese Herbal Medicine Research Articles

Chinese Herbs for Inducing Rat Bone Marrow Mesenchymal Stem Cells Differentiated into Neuron-Like Cells

The purpose of this study was to observe the influence of two Chinese herbs of ligustrazine and Xuefuzhuyu injection on neuron-like cells differentiation from rat bone marrow mesenchymal stem cells (BMSCs) respectively. Most primarily cultured BMSCs adhered to the wall at 3 days after cultured, which proliferated faster after passaged, and the 5th passage of cells were mostly purified into BMSCs. In the present study, the 5th passage of BMSCs were (97.51±1.22) % CD44 positive, but negative for CD45, which were identified by immunocytochemical technique. Serum-free low-sugar Dulbecco’s modified Eagle’s medium (L-DMEM) contains 1.25 g/L ligustrazine and 3.0 g/L Xuefuzhuyu injection were used to induce the 5th passage of BMSCs respectively in vitro. Neuron-like cells with prominence and bifurcation could be detected after induction under an inverted phase contrast microscope. The immunocytochemical method showed that nestin and neuron-specific enolase (NSE) were positive in neuron-like cells, but without glial fibrillary acidic protein (GFAP) expression. Both ligustrazine and Xuefuzhuyu injection have the potential for inducing neuron-like cells differentiation from rat bone marrow mesenchymal stem cells respectively. Compared with Xuefuzhuyu injection-induced cells, neuron-like cells induced with ligustrazine might be better in the level of morphological changes, as well as nestin and NSE expression.

Exploration on the corrosion inhibition performance of Salvia miltiorrhiza extract as a green corrosion inhibitor for Q235 steel in HCl environment

Salvia Miltiorrhiza, extensively distributed and commonly employed as a traditional Chinese medicinal herb, has garnered significant attention. In this study, the Salvia Miltiorrhiza extract (SME) was prepared by one-step water extraction method, and was firstly used as a novel corrosion inhibitor for Q235 steel in 1 mol/L HCl solution. As identified via liquid chromatography-mass spectrometry, the findings reveal that Salvianic acid A, tanshinone II A, danshenxinkun D, dihydrotanshinone, and methylene tanshinquinone are the primary constituents of SME. The optimum corrosion inhibition efficiency reached 92.8 % at 200 mg/L and maintained at 90.4 % after 72 h. Based on in-situ scanning vibration electrode technology (SVET) monitoring, the adsorption of inhibitor molecules on metal surface greatly retarded the propagation of localized corrosion. AFM examination of the corroded surface reveals that the samples supplemented with SME exhibit a smoother surface compared to the blank group. The force curve graph for the SME-added group demonstrates a more evenly distributed point array and an elevated average adhesion force, indicating that the addition of SME improves the corrosion resistance of the metal surface. XPS characterization illustrated that SME interacted with iron ions to form insoluble precipitate. This work investigated the application of SME as an eco-friendly corrosion inhibitor for carbon steel in acidic medium, providing a new approach for the high value-added utilization of Salvia Milliorrhiza.

Quality control of traditional Chinese medicine Chelidonii herba based on 2D-Q-NMR

Chelidonii herba is a traditional Chinese medicinal herb with effects including antispasmodic, analgesic, antitussive, and bronchodilator properties. Alkaloids are the main bioactive ingredients in Chelidonii herba. In this study, a two-dimensional nuclear magnetic resonance (Heteronuclear Singular Quantum Correlation, HSQC-2D-NMR) technique was employed to quantitatively analyze the total alkaloid content and three major active alkaloid monomers in Chelidonii herba from eleven different sources. The quantification results of the three monomeric alkaloids were also verified using conventional quantitative control methods such as HPLC. Experimental findings indicate that the total alkaloid content is not directly correlated with the content of the three monomeric alkaloids. Furthermore, the content of any individual monomeric alkaloid does not accurately reflect the overall quality of Chelidonii herba. It was demonstrated that the 2D-Q-NMR NMR can be applied as an alternative method. While maintaining the same levels of accuracy and precision, the 2D-Q-NMR method is simpler to operate and provides more comprehensive results with higher reproducibility in some cases.

Huangqi-Danshen Decoction Against Renal Fibrosis in UUO Mice via TGF-β1 Induced Downstream Signaling Pathway.

Huangqi-Danshen decoction (HDD) is a Chinese medicinal herb pair with good efficacy in treating chronic kidney disease, but its mechanism needs to be clarified. To uncover the underlying mechanism of HDD antagonizing renal fibrosis through network pharmacology (NP) analysis and experimental validation. The chemical components of water extract of HDD were analyzed by combining the ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrum analysis (UHPLC-QE-MS) and HERB database. NP was used to identify core common targets of HDD components and renal fibrosis. Subsequently, male C57BL/6 mice were divided into Sham, unilateral ureteral obstruction (UUO) and UUO+HDD groups. Renal function, histopathology, Western blotting, and immunohistochemistry analyses were used to evaluate the protective effect of HDD on UUO mice. The effects of HDD on signaling pathways were validated in both UUO mice and transforming growth factor-β1 (TGF-β1)-induced HK-2 cells. By combining UHPLC-QE-MS analysis and HERB database, 25 components were screened in HDD extract. There were 270 intersection targets of the 25 components and renal fibrosis. Based on their scores in protein-protein interaction analysis and degree values in component-pathway-target triadic network, 6 core common targets of the 25 components and renal fibrosis were identified, namely phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription 3(Stat3), non-receptor tyrosine kinase Src (Src), epidermal growth factor receptor (EGFR), matrix metalloproteinase 9 (MMP9), and MMP2. HDD ameliorated renal tubular damage and collagen deposition and downregulated fibrosis-related proteins expression in UUO mice. Furthermore, HDD was demonstrated to reduce PI3K, Stat3, Src, EGFR, and MMP2 expressions, and enhance MMP9 expression in the kidney of UUO mice and in TGF-β1-induced HK-2 cells. HDD can alleviate renal fibrosis which may be related to regulating the expression of essential proteins in the epithelial-mesenchymal transition and extracellular matrix production/degradation signaling pathways.

Species of Chinese materia medica resources based on the fourth national survey of Chinese materia medica resources

Species of Chinese materia medica resources based on the fourth national survey of Chinese materia medica resources

Exploring the Effects of Different Processing Techniques on the Antitussive Expectorant of Platycodon grandiflorus by Metabonomics and Pharmacologic Methods

Background and Purpose Platycodon grandiflorum is a traditional Chinese herbal medicine, which can disperse lung, promote pharynx, dispel phlegm and expel pus. Its processing history was first seen in the “Zhou Hou Bei Ji Fang” of the Jin Dynasty in China. Through processing, effective substances in plants can be enriched and negative substances can be reduced. Therefore, this study explored the effects of different processing methods on the antitussive and expectorant effects of Platycodon grandiflorum through metabolomics and pharmacology, aiming to provide a theoretical basis for clinical application. Experimental Approach The changes of metabolites before and after processing of Platycodon grandiflorum were analyzed by Nexera UHPLC LC-30A-HILIC-Orbitrap-Q Exactive HF-X platform. The antitussive and expectorant effects of processed Platycodon grandiflorum were verified by mouse concentrated ammonia induced cough method and tracheal phenol red drainage method. Key Results After processing, some metabolites of Platycodon grandiflorum changed, among which 24 kinds of terpenoid metabolites changed significantly. Through the experiment of ammonia-induced cough in mice and phenol red expectorant experiment, it was found that fresh JZI 40%, fresh CZ 80%, dry JZZ 40% and dry JZI 80% had obvious antitussive effect, and dry JZZ 40% had obvious expectorant effect. Conclusions and Implications Some processing methods can indeed further improve the antitussive and expectorant effects of Platycodon grandiflorum, which may be due to the effect of increasing the content of triterpenoids after processing, but the mechanism of processing to improve the effect of relieving cough and expectorant needs further study.

P38 Signaling Mediates Naringin-Induced Osteogenic Differentiation of Porcine Metanephric Mesenchymal Cells.

To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism. Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin. Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(-). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.

Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis

Hepatic ischemia/reperfusion injury (HIRI) is a common pathophysiological condition occurring during or after liver resection and transplantation, leading to hepatic viability impairment and functional deterioration. Recently, ferroptosis, a newly recognized form of programmed cell death, has been implicated in IRI. Rehmanniae Radix Praeparata (RRP), extensively used in Chinese herbal medicine for its hepatoprotective, anti-inflammatory, and antioxidant properties, presents a potential therapeutic approach. However, the mechanisms by which RRP mitigates HIRI, particularly through the regulation of ferroptosis, remain unclear. In this study, we developed a HIRI mouse model and monocrotaline (MCT)- and erastin-induced in vitro hepatocyte injury models. We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI. The RRP aqueous extract was characterized by the presence of acteoside, rehmannioside D, and 5-hydroxymethylfurfural. Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress, reduced intracellular iron accumulation, and attenuated HIRI-induced liver damage. Additionally, RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro. Mechanistically, the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake, promoting hepcidin- and ferroportin-mediated iron efflux, and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression. Moreover, siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract’s inhibitory effect on ferroptosis. In conclusion, our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI, highlighting the restoration of iron metabolic balance. These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

The cluster analysis of traditional Chinese medicine authenticity identification technique assisted by chemometrics

This study explore the authenticity identification technique of traditional Chinese medicine (TCM) using chemometrics in conjunction with cluster analysis. A clustering Gaussian mixture model was constructed and applied for the data clustering analysis of four types of TCM. Chemical measurements combined with discrete wavelet transform (DWT), Fourier transform infrared spectroscopy (FTIR), and Fourier self-deconvolution (FSD) were utilized for the detailed differentiation of Bupleurum scorzonerifolium, Bupleurum yinchowense, Bupleurum marginatum, and Bupleurum smithii Wolff var. parvifolium. Differences in the attenuated total reflection-FTIR (ATR-FTIR) spectra among the four TCMs were observed. Utilizing clustering algorithms, the one-dimensional DWT of the infrared spectra of samples was employed for the authentication of Chinese herbal medicines. The model demonstrates optimal performance throughout 2000 rounds of network training. The accuracy (88.6 %), sensitivity (86.5 %), and specificity (82.7 %) of the model constructed in this study significantly surpassed those of the CNN model: accuracy (67.7 %), sensitivity (70.4 %), and specificity (68.5 %) (P < 0.05). By setting the cluster size K = 5 and the number of Gaussian mixture model components to 5, the model effectively fits the actual number of categories within the dataset. Infrared spectroscopy analysis revealed distinct carbon-oxygen stretching vibration absorption peaks between 1025 and 1200 cm−1 for Bupleurum scorzonerifolium, Bupleurum yinchowense, Bupleurum marginatum, and Bupleurum smithii Wolff var. parvifolium, indicating strong absorption peaks of carbohydrates. A comprehensive structural information analysis revealed a similarity of above 0.982 among the four types of TCM. Combined with chemometrics and intelligent algorithm-based cluster analysis, successful and accurate authentication of TCM authenticity was achieved, providing an effective methodology for quality control in TCM.

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside–stimulated dental pulp stem cells-derived exosomes for wound healing and bone regeneration

Background/purpose-2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is a bioactive component in the Chinese herb Polygonum multiflorum, recognized for its anti-inflammatory and lipid-lowering properties. Human dental pulp stem cells (hDPSCs) have excellent capabilities in tooth regeneration, wound healing, and neural repair. The exosomes (Exo) released by hDPSCs contain bioactive molecules that influence cell proliferation, differentiation, and immune responses. Therefore, we aimed to unveil the potential of THSG-Exo and evaluate its regenerative capabilities through the in vitro experiment and rat bone defect model. Materials and methodsThe effects of hDPSC-derived exosomes, with or without THSG treatment, on repair and bone regeneration were evaluated through in vitro and in vivo studies. Finally, we conducted a proteomic analysis to meticulously compare the compositional contents of the two types of exosomes. ResultsIn vitro data showed that 10 and 100 μM THSG-Exo enhanced cell proliferation and osteogenic differentiation, reducing wound size to 40 % of its original size. In our maxillary bone defect rat model, THSG-Exo significantly increased bone volume, trabecular thickness, and bone density in the bone defect area. In addition, proteomic analysis of THSG-Exo revealed diverse proteins linked to bone differentiation and tissue repair, including bone morphogenetic protein-1 (BMP-1) and tumor necrosis factor (TNF)-α-stimulated gene 6 (TNFAIP6). Our searches in functional databases revealed that THSG-Exo is involved in numerous biological pathways. ConclusionTHSG-Exo enhanced cell proliferation, wound healing, and osteogenesis in vitro, while also expediting tissue repair and bone regeneration in vivo. The protein diversity of THSG-Exo contributes significant value in both basic and regenerative medicine.

Hepatocyte aquaporin 8-mediated water transport facilitates bile dilution and prevents gallstone formation in mice

Although water channel aquaporin-8 (AQP8) has been implicated in hepatic bile formation and liver diseases associated with abnormal bile flow in human and animal studies, direct evidence of its involvement in bile secretion is still lacking. This study aimed to determine the role of AQP8 in bile secretion and gallstone formation. We generated various transgenic knock-in and knockout mouse models and assessed liver AQP8 expression by immunostaining and immunoblotting, hepatic bile secretion by cannulation of the common bile duct, cholesterol gallstone formation by feeding a high-fat lithogenic diet, and identified regulatory small molecules by screening the organic fractions of cholagogic Chinese herbs and biochemical characterization. We identified a novel expression pattern of AQP8 protein in the canalicular membrane of approximately 50% of the liver lobules. AQP8-deficient mice exhibited impaired hepatic bile formation, characterized by the secretion of concentrated bile with a lower flow rate and higher levels of bile lipids than that of wild-type littermates. AQP8-/- mice showed accelerated gallstone formation, which was rescued by AAV-mediated hepatic expression of AQP8 or AQP1. Moreover, we identified a small molecule, scutellarin, that upregulates hepatocyte AQP8 expression in vitro and in vivo. In AQP8+/+ mice, scutellarin significantly increased bile flow, decreased bile lipid concentrations, and prevented gallstone formation compared to AQP8-/- mice. Molecular studies revealed that scutellarin promoted the ubiquitination and degradation of HIF-1α, a transcriptional negative regulator of AQP8, by disrupting its interactions with HSP90. AQP8 plays a crucial role in facilitating water transport and bile dilution during hepatic bile formation, thereby mitigating gallstone formation in mice. Small-molecule intervention validated hepatocyte AQP8 as a promising drug target for gallstone therapy. The incidence of gallstone disease is high, and current drug treatments for gallstones are very limited, necessitating the identification of novel drug targets for developing new drugs with universal applicability. To our knowledge, this is the first study to provide direct evidence that hepatic water channel AQP8 plays a key role in bile dilution and gallstone formation. Modulation of hepatic water transport may provide a universal therapeutic strategy for all types of gallstone diseases.

Multi-faceted potential of sophoridine compound's anti-arrhythmic and antioxidant effects through ROS/CaMKII pathway

Cardiac arrhythmias remain a significant cause of mortality and morbidity, for novel antiarrhythmic therapies. This study states that the first report of sophoridine (SPN), a quinolizidine alkaloid derived from traditional Chinese herbs, shows promise as a potential candidate due to its anti-arrhythmic and antioxidant properties. The study found that cell viability in H9C2 rat cardiomyocytes remained stable even when treated with SPN at a higher dosage of 100 μg/ml. This phenomenon was accompanied by increases in mitochondria-derived reactive oxygen species (ROS) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, at 50 and 100 μg/ml. Glucose fluctuations regulate ventricular arrhythmias caused by SPN by activating the ROS/CaMKII pathway. Experimental models using zebrafish provided additional evidence supporting the regulatory effects of SPN on heart rate. In addition, the administration of SPN resulted in substantial deregulation of crucial genes involved in heart development (nppa, nppb, tnnt2a) at the transcriptional level in zebrafish. These findings provide insight into the various pharmacological properties of SPN and this opens up new possibilities for anti-arrhythmic treatment strategies.

ER stress modulates Kv1.5 channels via PERK branch in HL-1 atrial myocytes: Relevance to atrial arrhythmogenesis and the effect of tetramethylpyrazine

Endoplasmic reticulum (ER) stress is implicated in cardiac arrhythmia whereas the associated mechanisms remain inadequately understood. Kv1.5 channels are essential for atrial repolarization. Whether ER stress affects Kv1.5 channels is unknown. This study aimed to elucidate the response of Kv1.5 channels to ER stress by clarifying the unfolded protein response (UPR) branch responsible for the channel modulation. In addition, the effect of tetramethylpyrazine (TMP) on Kv1.5 channels was studied. Patch clamp and western-blot results revealed that exposure of HL-1 atrial myocytes to ER stress inducer tunicamycin upregulates Kv1.5 expression, increases Kv1.5 channel current (IKur) (14.91 ± 1.11 vs. 6.11 ± 1.31 pA/pF, P < 0.001), and shortened action potential duration (APD) (APD90: 82.79 ± 5.25 vs.121.11 ± 6.72 ms, P < 0.01), which could be reverted by ER stress inhibitors. Blockade of the PERK branch while not IRE1 and ATF6 branches of UPR downregulated Kv1.5 expression, accompanied by a decreased IKur (9.03 ± 0.99 pA/pF) and a prolonged APD90 (113.69 ± 4.41 ms) (P < 0.01). PERK-mediated increases of Kv1.5 expression and IKur were also observed in HL-1 cells incubated with thapsigargin. TMP suppressed the enhancement of IKur (10.52 ± 0.97 vs. 17.52 ± 2.25 pA/pF, P < 0.05), prevented the shortening of APD (APD90: 110.16 ± 5.36 vs. 84.84 ± 4.58 ms, P < 0.05), and inhibited the upregulation of Kv1.5 triggered by ER stress. Our study suggests that ER stress induces upregulation and activation of Kv1.5 channels in atrial myocytes through the PERK branch of UPR. TMP prevents Kv1.5 upregulation/activation and the resultant APD shortening by inhibiting ER stress. These results may shed light on the mechanisms of atrial arrhythmogenesis and the antiarrhythmic effect of the traditional Chinese herb TMP.

Gastrodin attenuates high fructose-induced sweet taste preference decrease by inhibiting hippocampal neural stem cell ferroptosis

IntroductionHigh fructose intake has been implicated as a risk factor for behavioral disorders, potentially through cell ferroptosis induction in the central nervous system. Neural stem cells (NSCs) are crucial for maintaining hippocampal neurogenesis to resist behavioral alterations. Gastrodin, derived from the traditional Chinese herb Gastrodia elata, has neuroprotective effect. ObjectivesThis study aimed to elucidate the underlying mechanism by which high fructose induces sweet taste preference and assesses the impact of gastrodin on hippocampal NSC ferroptosis. MethodsMice and cultured NSCs were treated with high fructose and/or gastrodin, respectively. NSC ferroptosis was evaluated by assay of lipid peroxidation and DNA double-strand breaks. Transcriptome sequencing (RNA-seq), Western blotting, and chromatin immunoprecipitation (ChIP) were employed to explore the potential mechanism underlying high fructose-induced NSC ferroptosis and the modulation of gastrodin. Simultaneously, specific gene expression was regulated by lentivirus injection into the hippocampus of mice. ResultsOur data showed that gastrodin mitigated sweet taste preference decline and hippocampal NSC ferroptosis in high fructose-fed mice, being consistent with reduction of reactive oxygen species (ROS) and iron accumulation in hippocampal NSC mitochondria. Mechanistically, we identified CDGSH iron-sulfur domain 1 (CISD1) as a mediator of NSC ferroptosis, with its expression being augmented by high fructose. Overexpression of Zic family member 2 (ZIC2) increased the transcription of Cisd1 gene. Additionally, overexpression of Zic2 with lentiviral vectors in hippocampus showed the decreased sweet taste preference in mice, consistently up-regulated CISD1 protein expression and reduced hippocampal NSC number. Gastrodin downregulated ZIC2 expression to inhibit CISD1 transcription in its attenuation of high fructose-induced NSC ferroptosis and sweet taste preference decrease. ConclusionCollectively, high fructose can drive hippocampal NSC ferroptosis by upregulating ZIC2 and CISD1 expression, thereby contributing to the decline in sweet taste preference. Gastrodin emerges as a promising agent for mitigating NSC ferroptosis and improving sweet taste preference.

Discovery and characterization of naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from the antiviral herb Ephedra

The Chinese herb Ephedra (also known as Mahuang) has been extensively utilized for the prevention and treatment of coronavirus-induced diseases, including coronavirus disease 2019 (COVID-19). However, the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully elucidated. The main protease (Mpro) of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle, making it a critical target for the development of antiviral therapies. This study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from Ephedra and to investigate their covalent binding sites. The results demonstrated that the non-alkaloid fraction of Ephedra (ENA) exhibited a potent inhibitory effect against the SARS-CoV-2 Mpro effect, whereas the alkaloid fraction did not. Subsequently, the chemical constituents in ENA were identified, and the major constituents’ anti-SARS-CoV-2 Mpro effects were evaluated. Among the tested constituents, herbacetin (HE) and gallic acid (GA) were found to inhibit SARS-CoV-2 Mpro in a time- and dose-dependent manner. Their combination displayed a significant synergistic effect on this key enzyme. Additionally, various techniques, including inhibition kinetic assays, chemoproteomic methods, and molecular dynamics simulations, were employed to further elucidate the synergistic anti-Mpro mechanisms of the combination of HE and GA. Overall, this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from Ephedra and characterizes their synergistic anti-Mpro synergistic effect, providing robust evidence to support the anti-coronavirus efficacy of Ephedra.

RETRACTION: Effect of Chinese herbal compound dressings in treating patients with diabetic foot ulcers: A meta-analysis.

Retraction: Q. Yang , F. Liu , C. Zhao , X. Xu , Y. Wang , W. Zuo , "Effect of Chinese Herbal Compound Dressings in Treating Patients with Diabetic Foot Ulcers: A Meta-Analysis," International Wound Journal 21, no. 3 (2023): e14767, https://doi.org/10.1111/iwj.14767. The above article, published online on 05 March 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor in Chief, Professor Keith Harding; and John Wiley & Sons, Ltd. It came to the publisher's attention from a third party that a number of articles shared concerning similarities in format and structure. Following an investigation by the publisher, the retraction has been agreed on as the peer review and publishing process for this article were found to be manipulated.

Evaluation of the Pharmaceutical Activities of Chuanxiong, a Key Medicinal Material in Traditional Chinese Medicine.

Szechwan lovage rhizome (SLR, the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained.

The Inhibitory Impact of a Co-Assembly Gel with Natural Carrier-Free Binary Small Molecules, as Used in Traditional Chinese Medicine, on the Viability of SW1990 Cells.

Chinese herbs are a huge treasure trove of natural products and an important source of many active molecules. The theory of traditional Chinese medicine compatibility (TCMC) is widely applied in clinical practice, but its mechanism is still ambiguous. This study aims to open a new window for this predicament by studying the interaction between the main active ingredients from a drug pair. Carrier-free assembly of natural products improves the shortcomings of traditional nanodelivery systems and opens a new path for the development of new nanomaterials. The drug pair "Pueraria and Hedyotis diffusa" has been commonly used in clinical practice, with a predominant therapeutic effect. This study is devoted to the study of the binary small molecule co-assembly of the main active molecules from the drug pair. In this study, we introduce a carrier-free composite gel, formed by the co-assembly of puerarin (PUE) and deacetylasperulosidic acid (DAA) via non-covalent bonds including π-π packing, intermolecular hydrogen bonding, and C=O π interactions. With a strain point 7-fold higher than that of P gel, the P - D gel exhibited favorable rheological properties. The survival rate of SW1990 cells in the P - D group was only 21.39% when the concentration of administration reached 200 μM. It thus demonstrated activity in inhibiting SW1990 cells' survival, suggesting potential in combating pancreatic cancer. Furthermore, this research offers a valuable concept for enhancing the mechanical properties and bioactivity of hydrogel materials through the utilization of a multi-component natural small molecule co-assembly approach. More importantly, this provides new ideas and methods for the treatment of pancreatic cancer and the analysis of traditional Chinese medicine compatibility theory.

A Novel 3-Benzyloxychromone From Celastrus orbiculatus Thunb. Exhibits Anticancer Effects on Non-Small Cell Lung Cancer Cells via GSK-3β-Dependent c-Jun/ATF2 Pathway.

Celastrus orbiculatus Thunb. is a vine used as a traditional Chinese medicinal herb. In this study, we focused on the anticancer cytotoxicity and underlying mechanism of previously unreported 3-oxygen-substituted isoflavone analogue (3-benzyloxychromone, 3-Boc) from the herb. Initially, we established cell line-derived xenograft mouse model using H1299 non-small cell lung cancer (NSCLC) cells and found that the ethanol crude extracts of the stem part of C. orbiculatus (200 mg/kg) could substantially suppress the growth of xenograft tumors in athymic nu/nu mice. We compared 3-Boc with three other flavonoid analogues isolated from the stem part of C. orbiculatus. Among these, 3-Boc showed the most potent cytotoxicity against H1299 and H1975 NSCLC cells. Colony formation, EdU incorporation and Annexin V-FITC/PI apoptosis assays demonstrated that 3-Boc induced growth inhibition primarily by inhibiting DNA replication and inducing apoptotic death of NSCLC cells. Structure-based target prediction and MD simulation suggested that 3-Boc potentially suppressed the activity of glycogen synthase kinase-3β (GSK-3β) by interacting with the ATP-binding site. Western blot analysis indicated that 3-Boc triggered the phosphorylation of Serine 21 of GSK-3α or Serine 9 of GSK-3β in a time- and dose-dependent manner. To investigate the dependency of GSK-3β, we established GSK-3β knockout in H1299 cells. Depletion of GSK-3β enhanced 3-Boc-induced cytotoxicity compared with wild-type counterparts through activated c-Jun/ATF2 signaling pathway. Altogether, our study highlights the anticancer potential of C. orbiculatus and the discovery of novel 3-oxygen-substituted chromone from the herb, which may have important implications for screening promising modulators of GSK-3β and related signaling pathways in the treatment of cancer.

Knockdown and Overexpression Experiments to Investigate the Inhibitory Mechanism of Fuzheng Xiaozheng Prescription, an Effective Chinese Herbal Formula for the Clinical Treatment of Hepatocellular Carcinoma.

Fuzheng Xiaozheng prescription (FZXZP) is an effective formula for the treatment of different kinds of chronic liver diseases. However, its potential molecular mechanisms in treating hepatocellular carcinoma (HCC) have not been investigated thoroughly. The aim of this study is to elucidate the targets and intrinsic mechanisms of FZXZP and their active components for the treatment of HCC. The efficacy of FZXZP against HCC was clarified through a rat HCC model and HCC cell culture. Network pharmacology and molecular docking were utilized to predict the mechanism of action and effector components of FZXZP. The key mechanism and targets were verified by the construction of overexpression and knockout cell models. The results showed that FZXZP greatly delayed the development of HCC in vivo experiments, as evidenced by biochemical evaluations, H&E analyses and growth inhibition of HCC. FZXZP dramatically inhibited cell viability and proliferative capacity and induced the apoptosis of hepatoma cells in vitro. Moreover, network pharmacology analyses demonstrated that the EGFR family and apoptosis-related targets were found to be the most significant in bioinformatics analysis. Furthermore, the EGFR/STAT3 signal axis might be the most likely target of FZXZP in anti-HCC due to the fact that it could be down-regulated by FZXZP with an upward trend of Bax, Caspase-3, Caspase-8, Caspase-9 and an inverse trend of Bcl2. Importantly, the above targeted signal axis was finally validated by our knockdown and overexpression analyses. Meanwhile, flow cytometry and TUNEL staining also revealed that FZXZP significantly induced apoptosis in the EGFR-overexpressing HCC cell line. The molecular docking results revealed that the key effector components of FZXZP that exerted the above regulatory roles were wogonin and glycitein. All of these results suggest that FZXZP could significantly delay HCC development by inhibiting proliferation and promoting apoptosis of HCC cells, and the EGFR/STAT3 signal axis might be a critical signal axis of FZXZP in suppressing HCC progression.