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Objective(s): Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism. Materials and Methods: Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot. Results: Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1β, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression. Conclusion: These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.

Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the molecular mechanisms of Huangqi {Astragalus) in the treatment of premature ovarian insufficiency (POI) using network pharmacology and molecular docking methods. Methods: The active compounds and target proteins of Huangqi were screened from the TCMSP database, while the disease target proteins associated with POI were obtained from the Genecards database. The Venny online tool was used to identify the overlapping genes between the two datasets. Cytoscape software was used to construct a gene regulatory network for the active ingredients of Huangqi. The protein-protein interaction (PPI) network and core genes were selected based on the STRING database and CytoNCA plug-in of Cytoscape. GO (gene ontology) enrichment and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses of the overlapping genes were performed using the DAVID database. Molecular docking techniques were used to further elucidate the molecular mechanisms underlying the therapeutic effects. Human ovarian granulosa-like tumor cells (KGN) underwent serum starvation (SS) treatment to induce POI cell models and then received quercetin treatment, and experimentally validated the network pharmacology prediction results by TUNEL staining and Western blotting assay. Results: The TCMSP database provided 32 active compounds and 552 target genes associated with Huangqi, while totally 730 disease target genes associated with POI were screened out from the disease database. Of these, 62 genes were found to be shared between the two datasets. The top 6 compounds based on degree values were quercetin, isorhamnetin, kaempferol, mairin, formononetin and astragaloside IV. The 10 core genes identified were ALB, INS, AKT1, ACTB, TP53, TNF, ESR1, CASP3, STAT3 and PTEN. These potential targets were mainly involved in regulating the JAK2/STAT3 and PI3K/Akt signaling pathway. Molecular docking results revealed strong binding interactions between the compounds and the key proteins STAT3 and Akt1 in the JAK-STAT and PI3K-Akt signalling pathways. The results of in vitro experiments revealed that quercetin could activate the JAK2/STAT3 pathway and inhibit cell apoptosis. Conclusions: Network pharmacology and molecular docking analysis showed that Astragalus could regulate the response of ovarian cells to estradiol, inhibit apoptosis and regulate the JAK-STAT and PI3K-Akt signalling pathways in the treatment of early onset ovarian dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Background According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti‐tumor activity associated with Qi‐supplementing herbs, specifically the paired use of Huangqi and Danggui. Methods Analysis of compatibility regularity was conducted to screen the combination of Qi‐supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti‐tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti‐tumor activity and the mechanism of the active ingredients were verified by molecular experiments. Results There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti‐tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti‐tumor effects of the extract. Conclusions The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Globally, cervical cancer poses a substantial public health challenge, with low and middle-income countries bearing the highest burden [Rajkhowa, P., D.S. Patil, S.M. Dsouza, P. Narayanan and H. Brand. Evidence on factors influencing HPV vaccine implementation in South Asia: a scoping review. Glob. Public Health 18: 2288269, 2023]. The incidence rate ranks second highest among female malignant tumors in China, following only breast cancer. The prognosis of advanced cervical cancer is extremely poor, with a 5-year progression-free survival (PFS) rate of only 15%, and the treatment of advanced recurrent or metastatic cervical cancer remains a huge challenge. An increasing amount of evidence suggests that traditional Chinese medicine (TCM) can significantly enhance sensitivity to chemotherapeutic drugs, strengthen antitumor effects, and notably improve adverse reactions associated with cancer such as fatigue and bone marrow suppression. In recent years, the therapeutic effects and mechanisms of Chinese herbal medicines, such as the Guizhi-Fuling-decoction, the compound Yangshe granule, Huangqi, and Ginseng, herbal monomers (e.g., Ginsenoside Rh2, Tanshinone IIA, and Tetrandrine), and the related extracts and compound formulations, have received extensive attention for the treatment of cervical cancer. This paper reviews the research progress of TCM in cervical cancer. In addition, we reported a case of an advanced cervical cancer patient with multiple abdominal and pelvic metastasis who initially received chemotherapy, was then treated with TCM alone, and subsequently survived for 22 years. The model of whole-process management with TCM can enable more cancer patients to obtain longer survival periods. [ABSTRACT FROM AUTHOR]

The aim of this systematic review is to study the effects of Astragalus membranaceus (Huangqi) supplementation for sports activity and physical performance. PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar were systematically searched for relevant studies from inception up until October 2023. Eleven clinical studies were considered eligible for inclusion (six of them involved the administration of Huangqi alone, while, in the remaining trials, this herb was supplemented in combination with other remedies). On average, the number of study participants ranged from 8 to 120, and the sports activities practiced by the subjects included martial arts, mountain hiking, basketball, rowing, running, aerobic exercises, and strength training. When a dried extract was used, Astragalus was taken at a daily dose of 1 to 4 g for several weeks. Huangqi supplementation was associated with improvements in aerobic performance, oxidative status, reticulocytes percentage, and response to acclimatization, without a specific effect on the athletes’ strength. Better post-exercise immune functions were also observed, especially with regard to NK cell activity, IL-2 levels, CD4+/CD8+ ratio, and lymphocyte turnover. No adverse effects were described. In conclusion, Astragalus supplementation has the potential to decrease fatigue, enhance aerobic performance, and mitigate post-exercise immune suppression in athletes. It is advisable to conduct additional research on the subject to enhance the robustness of the existing evidence through larger-scale controlled trials.

The aim of this systematic review is to study the effects of Astragalus membranaceus (Huangqi) supplementation for sports activity and physical performance. PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar were systematically searched for relevant studies from inception up until October 2023. Eleven clinical studies were considered eligible for inclusion (six of them involved the administration of Huangqi alone, while, in the remaining trials, this herb was supplemented in combination with other remedies). On average, the number of study participants ranged from 8 to 120, and the sports activities practiced by the subjects included martial arts, mountain hiking, basketball, rowing, running, aerobic exercises, and strength training. When a dried extract was used, Astragalus was taken at a daily dose of 1 to 4 g for several weeks. Huangqi supplementation was associated with improvements in aerobic performance, oxidative status, reticulocytes percentage, and response to acclimatization, without a specific effect on the athletes' strength. Better post-exercise immune functions were also observed, especially with regard to NK cell activity, IL-2 levels, CD4+/CD8+ ratio, and lymphocyte turnover. No adverse effects were described. In conclusion, Astragalus supplementation has the potential to decrease fatigue, enhance aerobic performance, and mitigate post-exercise immune suppression in athletes. It is advisable to conduct additional research on the subject to enhance the robustness of the existing evidence through larger-scale controlled trials. [ABSTRACT FROM AUTHOR]

Huangqi (Astragalus spp.) is a versatile herb that possesses several therapeutic effects against a variety of diseases, especially lung diseases. The aim of this study was to establish a core collection of Astragalus germplasm resources based on 10 simple sequence repeat (SSR) markers. We used 380 samples of Astragalus collected from different regions to a core Astragalus collection using five different methods, including PowerCore-based M strategy, CoreFinder-based M strategy, Core Hunter-based stepwise sampling, PowerMarker-based simulated annealing algorithm based on allele maximization, and PowerMarker-based simulated annealing algorithm based on maximizing genetic diversity. Among these methods, the CoreFinder-based M strategy was found to be the most suitable approach as it preserved all the alleles, and most of the genetic diversity parameters of the constructed core collections were higher than those of the initial collection. Additional analyses demonstrated that the genetic diversity of the core collection was similar to that of the initial collection. Further, phylogenetic trees indicated that the population structure of the core collection was similar to that of the initial collection. In addition, our results showed that the optimal grouping value of K was 2. The construction of a core collection is beneficial for the understanding, management, and utilization of Astragalus. Moreover, this study will serve as a valuable reference for constructing core collections of other plants and fungi. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus is a medicinal herb extensively used in China. R2R3-MYB is one of the largest transcription factor families in plants, playing a key role in plant development and environmental stress responses. Although quite a few R2R3-MYB transcription factors from economic plants have been characterized, the biological roles of the R2R3-MYB genes in A. membranaceus remain largely unknown. Here, 123 AmR2R3-MYB members in A. membranaceus were systematically identified and their phylogenetic positions, protein and gene structures, and expression patterns were analyzed. Co-expression network analysis revealed that AmMYB82 was a key gene in regulation of flavonoid synthesis. AmMYB82 was found to localize in the nucleus and activated transcription of AmCHS. In the AmMYB82 overexpressing Arabidopsis thaliana , the content of total flavonoids increased, and the expression levels of six enzyme coding genes for flavonoid synthesis, including AmPAL , AmCHS , AmC4H , AmFLS , AmF3H , and Am4CL , were elevated. Overexpression of AmMYB82 enhanced drought tolerance of Arabidopsis seedlings. Furthermore, overexpression of AmMYB82 in A. membranaceus hairy roots increased flavonoid concentration, transcription of the corresponding enzyme genes, and drought stress tolerance. Building on these findings, we developed a working model for AmMYB82 regulating flavonoid biosynthesis and contributing to the abiotic stress response of A. membranaceus. AmMYB82 directly activated enzyme coding genes in the flavonoid biosynthesis pathway such as AmCHS , promoting flavonoid accumulation and increasing drought tolerance. This research enhanced our knowledge of the biological functions of R2R3-MYB genes and provided candidate genes for the genetic breeding of A. membranaceus. [Display omitted] • A total of 123 R2R3-MYB members were identified and characterized in A. membranaceus. • All A. membranaceus R2R3-MYB were functionally classified based on phylogenetic tree. • Co-expression analysis revealed the role of AmMYB82 in flavonoid synthesis regulation. • AmMYB82 raised flavonoid level by activating CHS in A. thaliana and A. membranaceus. • AmMYB82 enhanced the tolerance to drought stress in A. thaliana and A. membranaceus. [ABSTRACT FROM AUTHOR]

Cerebral ischemia-reperfusion (I/R) injury is a common complication of ischemic stroke, with autophagy and pyroptosis playing key roles. Huangqi and Danggui (HQDG) are a commonly used drug pair of Chinese traditional medicine for clinical treatment of ischemic stroke. The study aims to investigate the interaction between autophagy and pyroptosis regulated by HQDG through the AMPK/mTOR signaling pathway during cerebral I/R injury. Model of middle-cerebral artery occlusion/reperfusion (MCAO/R) in SD rats was established using the Longa suture method. The components of traditional Chinese medicine were detected by liquid chromatography coupled to quadrupole orbitrap high resolution mass spectrometry (LC/MS). Neurological deficits were evaluated by neurological function score. Changes of cerebral blood flow were detected by a laser speckle blood flow imaging instrument. The volume of cerebral infarction was observed by 2,3,5-Chlorotriphenyltetrazolium (TTC) staining. The permeability of the blood-brain barrier was measured by Evans blue test. Neurovascular unit and autophagosomes in brain tissue were assessed by transmission electron microscopy. Neuronal pyroptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)/Caspase-1 staining. The expression of autophagy related proteins, pyroptosis related proteins, and AMPK/mTOR pathway related proteins were detected by Western blot. After cerebral I/R injury, autophagy and pyroptosis, were characterized by increased number of autophagosomes and pyroptosis cells, upregulated expression of Beclin 1, LC3-II/LC3-I, NLRP3, cleaved Caspase-1, IL-1beta, IL-18 proteins, and downregulated expression of P62 proteins. HQDG significantly improved neurological function, reduced the volume of cerebral infarction, increased cerebral blood flow, improved blood-brain barrier permeability and the function of neurovascular units. Autophagy was further activated and pyroptosis was significantly inhibited by HQDG, which promoted increased number of autophagosomes, enhanced expression of Beclin 1, LC3-II/LC3-I proteins, reduced expression of P62, NLRP3, cleaved Caspase-1, IL-1beta, and IL-18 proteins, and downregulated the number of pyroptosis cells. On the other hand, after administering 3-Methyladenine (3-MA) to inhibit autophagy, the above effects of HQDG were significantly inhibited. Besides, HQDG promoted AMPK phosphorylation, and weakened mTOR phosphorylation. However, after the administration of AMPK inhibitor Compound C, HQDG caused increase in Beclin 1 and LC3-II/LC3-I, reduced P62 and NLRP3, and cleaved Caspase-1 protein expression, whereas cerebral blood flow decreased. HQDG alleviated pyroptosis by promoting autophagy via AMPK/mTOR signaling pathway after middle-cerebral artery occlusion/reperfusion in rats, showing its potential for treatment of cerebral I/R injury in humans. [Display omitted] • The activation of autophagy suppresses pyroptosis. • AMPK/mTOR axis can regulate the crosstalk between autophagy and pyroptosis. • Drug pairs of Huangqi and Danggui have neuroprotective effects. • Drug pairs of Huangqi and Danggui can regulate autophagy and pyroptosis. [ABSTRACT FROM AUTHOR]

• Hypolycemic formulas may have an anti-AD effect. • The main pharmacological qualities were "cold" and "sweet" discovered by TCMISS. • Hypoglycemic TCMs targeted PTGS2, ACHE discovered by network pharmacology. • Huangqi-Gegen drug pair was screened out from hypoglycemic TCMs. • Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the production of ACHE and PTGS2 proteins, reducing 5-HT intake, and then decreasing aβ deposition. Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aβ) 1–42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aβ in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aβ-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi–Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aβ deposition in the brain of the CL2006 strain of C. elegans. Huangqi–Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aβ deposition. [Display omitted] [ABSTRACT FROM AUTHOR]

Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has strengthened vitality and multifunctional pharmacological activities, but limited empirical evidence is available to support its effects in muscular hypertrophy. It evokes skeletal muscle hypertrophy by increasing anabolic pathway, which is essential to prevent sarcopenia in elderly population. In this study, we examined the effects of AM on skeletal muscle hypertrophy by focusing on the molecular mechanism. We employed an in vitro model to investigate whether AM-treated skeletal muscle, as represented by myotube C2C12 cells, was hypertrophic, and to further investigate the efficacy of AM-activated phosphorylation of PI3K/Akt/mTOR signaling that must occur prior to myotube hypertrophy. The results showed that the myotubes formed larger multinucleated myotubes with increased diameter and thickness (1.16-fold relative to control group, p < 0.05). Administration of PI3K and mTOR inhibitors abolished AM-induced muscular hypertrophy. Moreover, AM-induced PI3K-mediated myotube hypertrophy was accompanied by the activation of Akt and mTOR signaling. We concluded that the AM is a nutritional activator to enhance muscular hypertrophy by increasing PI3K/Akt/mTOR signaling phosphorylation. As the AM is effective in myotube hypertrophy, AM and its derivatives may be promising candidates for ergogenic aid to prevent sarcopenia. [ABSTRACT FROM AUTHOR]

COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a , miR-148b , and miR-146a , which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 Mpro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases. [ABSTRACT FROM AUTHOR]

Objective We aimed to investigate the mechanisms underlying the effects of Huangqi and Ezhu combined with 5-fluorouracil (5-FU) in the treatment of colon cancer. Methods One male BALB/c mouse was used to generate the orthotopic tumor, and orthotopic tumor tissue was transplanted into 80 male BALB/c mice to establish the CT26. WT mouse model. These 80 mice were randomly divided into (i) the model group, (ii) the 5-FU group (25 mg/kg), (iii) the high-dose huangqi plus ezhu group (12 g/kg), (iv) the mid-dose huangqi plus ezhu group (6 g/kg), (v) the low-dose huangqi plus ezhu group (3 g/kg), (vi) the high-dose combination therapy group (12 g/kg + 25 mg/kg), (vii) the mid-dose combination therapy group (6 g/kg + 25 mg/kg), and (viii) the low-dose combination therapy group (3g/kg +25 mg/kg) (n = 10 mice per group). Treatment lasted for 3 weeks. The tumor inhibition rate was calculated by collecting tumors after the mice were killed. Chemokin (C-X-C) motif ligand 10 (CXCL10), Chemokin (C-X-C) motif receptor 3 (CXCR3), Chemokin (C-C) motif ligand 3 (CCL3), and Chemokin (C-C) motif receptor 5 (CCR5) mRNA and protein expression levels in tumor tissue, lymphoid tissue, and liver tissue were measured by RT-PCR and western blot, respectively. Results Compared with model group, the tumor inhibition rate in each treatment group was increased (P < 0.01). Compared with 5-FU group, the tumor inhibition rate of high-dose, mid-dose, low-dose huangqi plus ezhu, groups and high-dose, mid-dose, low-dose combination therapy group was decreased (P < 0. 01). Compared with the high-dose huangqi plus ezhu group, the tumor inhibition rate of high-dose combination therapy group was increased (P < 0. 01), and low-dose huangqi plus ezhu groups were decreased (P < 0. 01). Compared with mid-dose huangqi plus ezhu group, the tumor inhibition rate of low-dose huangqi plus ezhu group was decreased (P < 0. 01), and the mid-dose combination therapy group group was increased (P < 0. 01). Compared with the high-dose combination therapy group, the tumor inhibition rate of mid-dose combination therapy group was increased (P < 0. 01). Compared with mid-dose combination therapy group, the tumor inhibition rate of low-dose combination therapy group was decreased (P <0. 01). Compared with the low-dose combination therapy group, the tumor inhibition rate of low-dose huangqi plus ezhu group was decreased(P <0. 01). Compared with the model group, mRNA and protein levels of CXCL10, CXCR3, CCL3, and CCR5 were lower in each treatment group (P <0. 01). Compared with the 5-FU group, mRNA and protein levels of CXCL10, CXCR3, CCL3, and CCR5 were higher in the mid- and low-dose huangqi plus ezhu groups (P <0. 05, P <0. 01) and lower in the combination therapy groups (P <0. 01). Compared with the 5-FU group, the mRNA and protein levels of CCL3 in orthotopic tumor tissue, lymph node tissue, and liver tissue and the protein levels of CCR5 in the liver tissue of the high-dose huangqi plus ezhu group were increased (P <0. 01), and the mRNA levels of CXCL10 and CXCR3 in the high-dose huangqi plus ezhu group were increased (P <0. 05, P <0. 01). Compared with the high-dose huangqi plus ezhu group, mRNA and the protein levels of chemokines and receptors were decreased in the high-dose combination therapy group (P < 0. 05), the protein levels of chemokines and receptors in orthotopic tumor tissue and lymph node tissue were increased in the mid-dose and low-dose huangqi plus ezhu groups (P < 0. 05), the protein levels of CXCL10, CXCR3, and CCR5 in liver tissue were increased in the mid-dose and low-dose huangqi plus ezhu groups (P < 0. 05), the mRNA levels of chemokines and receptors were increased in the low-dose huangqi plus ezhu group(P <0. 05), and the mRNA levels of CXCR3, CCL3, and CCR5 were increased in the mid-dose huangqi plus ezhu group (P <0. 05). Compared with the mid-dose huangqi plus ezhu group, the mRNA and protein levels of chemokines and receptors were decreased in the mid-dose combination therapy group (P < 0. 05), the protein levels of chemokines and receptors in orthotopic tumor tissue were increased in the low-dose huangqi plus ezhu group (P < 0. 05), the protein levels of CXCL10 and CCL3 in lymph node tissue were increased (P < 0. 05), the protein levels of CXCL10 and CCR5 in liver tissue were increased (P <0. 05), and the mRNA levels of CXCL10 and CCL3 were increased in the low-dose huangqi plus ezhu group (P <0. 05). Compared with the high-dose combination therapy group, the mRNA and protein levels of chemokines and receptors were increased in the low-dose combination therapy group (P < 0. 05), the protein levels of CCL3 ad CXCL10 in orthotopic tumor tissue were increased in the mid-dose combination therapy group (P < 0. 05), the protein levels of CCR5, CXCL10, and CXCR3 in lymph node tissue were increased in the mid-dose combination therapy group(P <0. 05), the protein levels of CXCL10 and CXCR3 in liver tissue were increased in the mid-dose combination therapy group (P <0. 05), and the mRNA levels of CXCR3 were increased in the mid-dose combination therapy group (P <0. 05). Compared with the mid-dose combination therapy group, the protein levels of CXCL10, CXCR3, and CCR5 in orthotopic tumor tissue were increased in the low-dose combination therapy group (P <0. 05), the protein levels of CXCL10 and CXCR3 in lymph node tissue were increased in the low-dose combination therapy group (P <0. 05), the protein levels of CXCR3 and CCR5 in liver tissue were increased in the low-dose combination therapy group (P < 0. 05), and the mRNA levels of CXCR3 and CCL3 were increased in the low-dose combination therapy group (P <0.05). Compared with the low-dose combination therapy group, the mRNA and protein levels of chemokines and receptors were increased in the low-dose huangqi plus ezhu group (P < 0. 05). Conclusions The combination of Huangqi and Ezhu can inhibit the proliferation of CT26. WT orthotopic tumors, and combination therapy with 5-FU could further enhance the efficacy. The underlying therapeutic mechanism may be related to the downregulation of the CXCL10/CXCR3 and CCL3/CCR5 axes, which are closely related to tumor invasion and metastasis. [ABSTRACT FROM AUTHOR]

COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a, miR-148b, and miR-146a, which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 Mpro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases.

Objective: To determine the therapeutic effect of Danggui Shaoyao San with Huangqi on rats with nephrotic syndrome (NS) was discussed, and the scientific connotation of TCM treatment principle was elaborated, so as to provide experimental basis for its clinical application. Methods: The NS rat model was established by iv administration of adriamycin; The rats were divided into model group, Danggui Shaoyao San group, Danggui Shaoyao San with Huangqi group, Huangqi group and positive drug group, with 10 rats in control group; The best dosage ratio of Danggui Shaoyao San and Huangqi was screened by Excel; 24 h urine protein was measured by BCA method; The electrolyte level was detected by automatic biochemical analyzer; In serum Urea nitrogen (BUN), Creatinine (SCr), Total cholesterol (TC), Triglyceride (TG), Total protein (TP), Albumin (ALB), Immunoglobulin M (Ig-M) and Immunoglobulin G (Ig-G) were detected by the kit; hematoxylin-eosin staining was used to observe the renal morphology; The Total water content (TBW), Extracellular water content (ECF) and Intracellular water content (ICF) were measured by experimental animal body composition analyzer. Results: Compared with the model group, the urine protein in the modified Astragalus group of Danggui Shaoyao Powder was significantly decreased (P < 0.01); Urine electrolytes were significantly decreased and serum electrolytes were significantly increased (P < 0.01); Serum BUN, SCR, TC and TG were significantly decreased (P < 0.01), while TP, ALB, TBW and ICF were significantly increased (P < 0.01); The levels of Ig-M and Ig-G were significantly increased (P < 0.01), TBW and ICF were significantly increased, and ECF was significantly decreased (P < 0.01); Histopathology showed that the pathological changes of renal tissue were obviously alleviated; The improvement of each index was better than that of Danggui Shaoyao San group and Huangqi group. Conclusion: Danggui Shaoyao San with Huangqi group can significantly improve the edema, proteinuria, blood lipid and immune function of NS rats, and the effect is better than that of Danggui Shaoyao San group and Huangqi group. It has the best therapeutic effect on NS, which indicates that Huangqi plays a key synergistic effect on Danggui Shaoyao San, which verifies the scientific connotation of "Yiqi Huoxue Lishui" in the treatment of NS. [ABSTRACT FROM AUTHOR]

Background: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui., Methods: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments., Results: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract., Conclusions: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Objective: To explore whether Huangqi-Honghua combination protect brain from cerebral ischemia reperfusion injury through promoting angiogenesis by inducing the Cav-1/VEGF(Caveolin-1/vascular endothelial growth factor) signal pathway. Methods:Sixty rats were randomly divided into five groups: control group, model group and Huangqi-Honghua 40:1, 20:1, 5:1 groups(12 rats per group). The rat cerebral ischemia reperfusion injury models were induced by nylon monofilament. After 21 days of administration, the neurological scores were evaluated, the infarct volumes were calculated. Immunohistochemical method was used to detect the microvessel density(MVD) in brain tissue. RT-PCR and Western-blotting was used to detect the m RNA and protein expression levels of Cav-1 and VEGF. Results: After 21 days of administration, the neurological scores of each group were decreased, especially the Huangqi-Honghua groups(P<0.01), and infarct volume(P<0.05~ P<0.01)in Huangqi-Honghua groups were significantly lower than the model group. Compared with model group, the level of MVD, Cav-1 and VEGF m RNA and protein expression levels were significantly higher in Huangqi-Honghua treatment group(P<0.05~ P<0.01). Conclusions: Huangqi-Honghua combination has protective against cerebral ischemia injury, the Cav-1/VEGF pathway may be involved and then promote the angiogenesis. Additionally, the best proportion of Huangqi-Honghua was 5:1. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV), a traditional Chinese medicine, is often used to treat cancer. Colorectal cancer imposes a heavy burden on patients and society. It is essential to update the clinical evidence supporting AS-IV in the treatment of colorectal cancer. The purpose of this review is to systematically evaluate the molecular pathway and safety of AS-IV in colorectal cancer. 7 databases were queried for Jan 2012-Dec 2022. A total of 37 related articles were retrieved. 8 papers were included to evaluate the role of AS-IV in colorectal cancer and make a review. AS-IV plays vital roles in colorectal cancer, especially in the suppression of proliferation, inducing tumor cell apoptosis, increasing immune function and reducing drug resistance. Furthermore, AS-IV has been proved to regulate many signaling pathways, which are usually affected by most cancers. However, a large-scale and well-designed multicenter randomized controlled study ensures that the safety and optimal dose of AS-IV will be determined in the future. [Display omitted] • This manuscript is the first systematic review to study the potential molecular pathways of astragaloside-IV in colorectal cancer. • The signal path figure found in the existing research for nearly 10 years was drawn in the manuscript. • AS-IV could be considered a Chinese traditional medicine with anti-colorectal cancer. • The safe and effective doses of AS-IV should be determined through large sample clinical studies in the future. [ABSTRACT FROM AUTHOR]

Background: HuangQi (HQ) is a major medicinal herb commonly used as an ingredient of traditional Chinese medicine (TCM) formulas. It has been proved to be effective against heart failure (HF). However, its holistic therapeutic mechanism is not yet well explored.Purpose: The present study was designed to investigate the inhibitory effects and action mechanism of HQ in adriamycin (ADR)-induced HF rats.Methods: An integrative approach combining comprehensive echocardiography index (CEI) and metabonomics was conducted to assess the integral efficacy of HQ against HF. CEI was constructed to comprehensively evaluate the protection of HQ through principal component analysis of eight echocardiography parameters. Meanwhile, NMR-based untargeted metabolomic studies were performed to investigate the regulative effects of HQ coupled with correlation analysis.Results: HQ showed significant regulatory effects on four echocardiography parameters (left ventricular diastolic diameter, left ventricular systolic wall thickness, ejection fraction and fractional shortening). The effect on comprehensive CEI also demonstrated the efficacy of HQ against HF, especially on the first principal component (PC1). HQ could exert marked metabolic regulations on five key metabolites related to HF (NAG, 3-hydroxybutyrate, glutamine, succinate and acetoacetate), which were mainly involved into alterations of energy metabolism, oxidative stress, hypertrophy, as well as inflammatory. Their correlation analysis revealed the relationship between the metabolic profiles and cardiac function, which further authenticated the systemic regulation of HQ against HF.Conclusion: Current evidences revealed that HQ was effective in control of HF from cardiac dysfunction and metabolic alterations. This study provided a useful approach for evaluating the efficacy of TCMs against HF. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus (AM) is a traditional Chinese medicinal herb, whose cytoprotective effects remain largely unknown. Here, the bacterial endotoxin lipopolysaccharide (LPS) was applied to a human pulmonary type II-like epithelial lung adenocarcinoma cell line, a human umbilical vein endothelial cell line, and a human bladder carcinoma cell line to construct in vitro models of intracellular oxidative stress. The authors assayed the cellular and mitochondrial cytoprotective effects of varying doses of AM root extract upon these cell lines. The cell lines were cultured as follows: LPS-only group, four LPS+AM groups treated with various AM concentrations plus LPS, and an untreated control group. Flow cytometry was used to assess apoptosis and cell cycle progression. A 2′,7′-dichlorofluorescein-diacetate assay was used to quantitate reactive oxygen species (ROS) generation. Mitochondrial membrane potential (Δψmit) was analyzed by Rhodamine 123 assay. Western blotting was performed to detect cleaved caspase-3, p53, and B cell lymphoma (Bcl)-2 levels. Across all cell lines, LPS significantly elevated apoptosis rates, shifted cells to S/G2 phase, increased ROS production, reduced Δψmit, upregulated cleaved caspase-3, upregulated p53, and downregulated Bcl-2 relative to controls (all P<0.05). As a general trend, increasing AM concentrations produced progressively greater reductions in the apoptosis rate, greater reductions in S/G2 phase %, greater reductions in ROS production, greater increases in Δψmit, greater reductions in cleaved caspase-3 and p53 expression, and greater increases in Bcl-2 expression. AM treatment protects human pulmonary and bladder epithelial cells, in addition to human endothelial cells, from LPS-induced apoptosis, in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

The Daodi herb, Huangqi from Shanxi, is derived from the root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. Huangqi was divided into different commercial specifications and grades in producing area according to macroscopic features. Developmental anatomy of anomalous structure of the perennial fresh main root of A. membranaceus var. mongholicus was investigated using conventional paraffin section to explore the relationship between anomalous structure and classification of commercial specifications and grades of Huangqi. The results of developmental anatomy showed that parenchyma cells in secondary phloem and secondary xylem of the perennial fresh main root regained meristematic ability, and resulted in anomalous structure. Several layers of additional periderm could sometimes be found in the secondary phloem near the initial periderm, which was called rhytidome. Additional periderm could sometimes be observed in the center of secondary xylem, which was described as "rotten heart." The area of rhytidome and "rotten heart" increased gradually with increasing age. The results of different commercial specifications and grades of Huangqi revealed rhytidome and "rotten heart" mainly existed in Ge‐Da‐Tou, Er‐Dao‐Tou, Hong‐Lan‐Qi, Special Class, First Class, and Second Class. The additional periderm in secondary phloem of Ge‐Da‐Tou, Er‐Dao‐Tou, Hong‐Lan‐Qi, and Special Class could reach five layers; however, that of First Class and Second Class was three layers at most. In summary, this study demonstrated the rules of the development of rhytidome and "rotten heart" in A. membranaceus var. mongholicus. The relationship between anomalous structure and different commercial specifications and grades of Daodi herb Huangqi, was clarified. Research highlights: The rhytidome and the development of "rotten heart" have not been reported in Astragalus membranaceus var. mongholicus. At present article, we demonstrated the developmental anatomy of the rhytidome and "rotten heart" existed in the secondary phloem and secondary xylem of the root of A. membranaceus var. mongholicus respectively. The rhytidome and "rotten heart" is different among six commercial specifications and grades of Huangqi. [ABSTRACT FROM AUTHOR]

The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.

Astragalus membranaceus (AM) is a popular “Qi-tonifying” herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of AM on ergogenic and anti-fatigue functions following physiological challenge. Male ICR strain mice were randomly assigned to four groups (n = 10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); and (3) exercise training with AM treatment at 0.615 g/kg/day (Ex-AM1) or (4) 3.075 g/kg/day (Ex-AM5). Both the vehicle and AM were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase after 15-min swimming exercise. Exercise training combined with AM supplementation increased endurance exercise capacity and increased hepatic and muscle glycogen content. AM reduced exercise-induced accumulation of the byproducts blood lactate and ammonia with acute exercise challenge. Moreover, we found no deleterious effects from AM treatment. Therefore, AM supplementation improved exercise performance and had anti-fatigue effects in mice. It may be an effective ergogenic aid in exercise training.

Huangqi (Astragali Radix), a traditional Chinese herb, is widely used in clinical therapy in China. In addition, an anti-allergic effect of constituents in Huangqi has been reported in the scientific literature. In the present study, cell membrane chromatography coupled online with UHPLC-ESI-MS/MS method was developed to screen, analyze and identify the anti-allergic components of Huangqi. The Laboratory of Allergic Disease 2 (LAD2) cell was used to establish cell membrane chromatography, which was combined with UHPLC-ESI-MS/MS. The coupled system was then used to screen anti-allergic components from Huangqi. Effects of active components were verified by histamine release assay. A component retained on the LAD2 cell membrane chromatography was identified as formononetin. Bioactivity of formononetin was investigated by histamine release assay in LAD2 cells, and it was found that formononetin could inhibit histamine release in a dose-dependent manner from 1 to 100 μ m. The LAD2 cell membrane chromatography online with UHPLC-ESI-MS/MS method is an effective technique for screening the anti-allergic components of Huangqi. [ABSTRACT FROM AUTHOR]

Background: Huangqi with the capacity to resist virus and preserve myocardium is a potential herb for treating patients with COVID-19 and related myocardial injury., Methods: We applied network pharmacology method and programming software including R and Perl to explore the probable mechanism of Huangqi fighting against the disease. Ingredients and target gene names of Huangqi were obtained from TCMSP database. Disease-associated genes were mined by searching GeneCards database. Venny online software was applied to draw Venn diagram of intersection genes. Cytoscape software was used to set up the network of disease, drug, compounds and targets. STRING database was applied to set up protein protein interaction (PPI) network. With intersection genes imported into WEBGESALT database, gene ontology (GO) analysis was completed. An R script basing on Kyoto Encyclopedia of Genes and Genomes (KEGG) database was applied to obtain KEGG pathways. Finally, we used AutoDockTools 1.5.6 software for molecular docking and PyMOL to visualize the docking details., Results: We obtained 20 active components and 18 potential target genes to construct a network, and found out quercetin and kaempferol were core ingredients. Key targets included EGFR, MAPK8, IL6, CASP3, RELA and PPARG. Huangqi showed its potential to reduce inflammatory response to prevent cytokine storm by inhibiting EGFR, IL6 and MAPK and protect myocardium by inhibiting apoptosis and oxidant stress. Huangqi may also work by adjusting ubiquitin and regulating multiple viral pathways., Conclusions: Huangqi may play a therapeutic role in treating COVID-19 with myocardial injury by the effects of resisting virus and protecting myocardium concurrently., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Context: Astragali Radix (Huangqi; Astragalus mongholicus BUNGE, Fabaceae) is used in herbal medicinal products as well as in many food supplements. In traditional Chinese medicine, the roots are used for its Qi tonifying, immunostimulant, cardioprotective, hepatoprotective and hypoglycemic effects. Objective: Astragaloside IV (AGS-IV), a cycloartane-type triterpene glycoside is used as a marker compound for the quality control of Astragali Radix in various pharmacopoeias. Materials and methods: In this study, we analyzed the content of AGS-IV and other astragalosides in various commercial samples of Huangqi by reversed-phase HPLC using evaporative light scattering detection. Results: The analyses revealed that AGS-IV is formed during sample preparation from acylated astragalosides like astragaloside I and astragaloside II, when using the assay method of the European Pharmacopoeia. Discussion and conclusion: For consistent assay results, the extraction methods of the pharmacopoeias should be re-evaluated and optimized. Alternatively, the hydrolysis by ammonia could be omitted and the genuine compounds like astragaloside I, II and malonyl-AGS-I could be considered for the quality control of Astragali Radix. [ABSTRACT FROM AUTHOR]

Astragali Radix (AR) is a popular traditional Chinese medicine that has been used for more than 2000 years. It is a well-known tonic for weak people with chronic diseases, such as heart failure and cerebral ischemia. Previous studies have reported that AR could support the "weak heart" of cancer patients who suffered from doxorubicin (DOX)-induced cardiotoxicity (DIC). However, the underlying mechanism remains unclear. This study aimed to uncover the critical pathways and molecular determinants for AR against DIC by fully characterizing the network-based relationship. We integrated ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) profiling, database and literature searching, and the human protein-protein interactome to discover the specific network module associated with AR against DIC. To validate the network-based findings, a low-dose, long-term DIC mouse model and rat cardiomyoblast H9c2 cells were employed. The levels of potential key metabolites and proteins in hearts and cells were quantified by the LC-MS/MS targeted analysis and western blotting, respectively. We constructed one of the most comprehensive AR component-target network described to date, which included 730 interactions connecting 64 unique components and 359 unique targets. Relying on the network-based evaluation, we identified fatty acid metabolism as a putative critical pathway and peroxisome proliferator-activated receptors (PPARα and PPARγ) as potential molecular determinants. We then confirmed that DOX caused the accumulation of fatty acids in the mouse failing heart, while AR promoted fatty acid metabolism and preserved heart function. By inhibiting PPARγ in H9c2 cells, we further found that AR could alleviate DIC by activating PPARγ to maintain fatty acid homeostasis. Our findings imply that AR is a promising drug candidate that treats DIC by maintaining fatty acid homeostasis. More importantly, the network-based method developed here could facilitate the mechanism discovery of AR therapy and help catalyze innovation in its clinical application. [Display omitted] • A network-based method was developed to explore the mechanism of AR against DIC. • Network analysis identified fatty acid metabolism as a putative curial pathway. • AR preserved heart function and promoted fatty acid metabolism on DIC mouse model. • AR alleviates DIC by stimulated PPARγ and then maintained fatty acid homeostasis. [ABSTRACT FROM AUTHOR]

This study evaluated the proliferation effects of huangqi on neuron regeneration. We investigated the molecular mechanisms, which include: (1) cyclin D1, A, E-cell cycle factors and MAPK signaling proliferation (2) FGF-2-UPA-MMPs migration signaling. After treatment with various Huanqi concentrations (1.25, 12.5, 125, 250 and 500 μg/ml,), we observed that Huanqi can increase Rsc 96 cell proliferation at 12.5 μg/ml (p < 0.01) concentration determined by the MTT and wound healing tests. Examination by RT-PCR and Western blotting assay showed that Huangqi is able to stimulate the mRNA and protein expressions of cyclin D1, A, E, cell cycle controlling proteins and excite ERK and P38 MAPK signaling pathways to promote cell proliferation. Huangqi stimulates the FGF-2-UPA-MMP 9 migration pathway and enhances RSC 96 Schwann cells migration. Using MAPK chemical inhibitors, U0126, SB203580 and SP600125, the proliferative effects of Huangqi on RSC 96 cells were ERK and P38 signaling-dependent. Based on these results, applying an appropriate dose of Huangqi with biomedical materials would be a potential approach to enhancing neuron regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Astragalus membranaceus is a common traditional Chinese medicinal plant widely used as a tonic to enhance the body''s natural defense mechanisms. In this study, bioactive fractions were isolated from the roots of Astragalus membranaceus. One of these fractions, designated as AI, was found to be the most potent with respect to its mitogenicity on murine splenocytes. Effects of AI on both specific and nonspecific immunity in mouse models were examined. Results showed that AI could exhibit mitogenic and co-mitogenic activities on mouse splenocytes, both in vitro and in vivo. Experiments in human cell culture demonstrated that AI was also active on human lymphocytes. It was found that AI was mitogenic to T cell depleted population but virtually inactive on B cell depleted population. Intraperitoneal injection of AI into mice markedly augmented the antibody response to sheep red blood cells. Besides, both the influx of macrophages into the peritoneal cavity and the phagocytic activity of macrophages were found to be enhanced by AI in vivo. On the other hand, AI could significantly increase the interleukin-2 receptor expression on mouse splenocytes in vitro. In terms of immunorestorative activity, it was found that AI could restore the lymphocyte blastogenic response of the older mice to values that are normally found in the younger mice. Moreover, administration of AI in vivo could partially restore the depressed immune functions in tumour-bearing mice and cyclophosphamide-treated mice. Collectively, the results clearly showed that AI could exhibit immunomodulating and immunorestorative effects, both in vitro and in vivo. [Copyright &y& Elsevier]

Abstract: Astragalus membranaceus, a commonly used Chinese medicinal plant, has been shown to be capable of restoring the impaired T cell functions in cancer patients. In this study, the in vitro and in vivo anti-tumor effects of A. membranaceus were investigated. Five bioactive fractions were isolated from the root of A. membranaceus, the fraction designated as AI was found to be the most potent among the five fractions with respect to its mitogenicity on murine splenocytes. Besides investigating the cytostatic effect of AI, its activities on macrophage function, tumor necrosis factor production, induction of lymphokine-activated killer cell and tumor cell differentiation were also examined. The macrophage-like tumors and the myeloid tumors were found to be more sensitive to the cytostatic activity of AI, whereas the fibroblast-like tumors and the mouse Ehrlich ascites tumor appeared to be relatively resistant. Moreover, AI could effectively suppress the in vivo growth of syngeneic tumor in mice. Results showed that murine macrophage pretreated with AI had increased in vitro and in vivo cytostatic activities towards MBL-2 tumor. AI could also act as a priming agent for tumor necrosis factor production in tumor-bearing mice. Preincubation of mouse splenocytes with AI could induce in vitro lymphokine-activated killer-like activity towards WEHI-164 cell. Furthermore, AI was able to induce monocytic differentiation of both human and murine cells in vitro. AI administered in vivo could even partially restore the depressed mitogenic response in tumor-bearing mice. Collectively, the results showed that A. membranaceus could exhibit both in vitro and in vivo anti-tumor effects, which might be achieved through activating the anti-tumor immune mechanism of the host. [Copyright &y& Elsevier]

Huangqi (HQ) is a commonly Chinese herb that has been widely used in China for thousands of years. Many classic traditional Chinese medicine (TCM) prescriptions consist of HQ, which is known as "eight Huangqi out of ten prescriptions". However, its contribution to the whole formula remains unclear. In this study, a classical prescription Huangqi jianzhong tang (HQJZ) was selected to evaluate the "monarch" role of HQ against chronic atrophic gastritis (CAG) rats based on pharmacology and metabonomic strategy. Traditional pharmacology indexes, including body weight variety, pathological examination and biochemical indexes of gastric juice showed that the efficacy of HQJZ and HQ were better than HY (HQJZ without HQ). Serum metabonomics analysis also showed that the same separation of metabolic features among them. 9 differential endogenous metabolites were screened and involved into the metabolic alterations induced by CAG. Among them, 7, 6 and 4 metabolites were regulated by HQJZ, HQ and HY, respectively. Three important pathways, including pyruvate metabolism, glycolysis or gluconeogenesis, aminoacyl-tRNA biosynthesis, were further screened out as the most important pathways related to the efficacy of HQ contributing to HQJZ by integrating MetaboAnalyst, systemsDock and binding ability weighted polypharmacology index (BAWP). Our work provided a novel method to study the metabolic contribution of HQ to the whole HQJZ in the treatment of CAG, which might be beneficial to understand the fundamental idea behind formula construction of TCM. • A first study to reveal the role of HQ contributing to HQJZ. • Metabolic pathway analysis integrating of metabonomics, molecular docking and BAWP. • Metabonomics approach applied in the TCM compatible study. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the third most prevalent cancer globally. In the treatment of CRC, surgical resection is commonly adopted, and neoadjuvant chemotherapy or immunotherapy is mainly administered for patients with advanced disease. However, despite the developments in the field of cancer treatment, the mortality rate of CRC has remained high. Therefore, novel treatments for CRC need to be explored. Astragalus membranaceus, commonly known in China as Huangqi (HQ), a traditional Chinese medicine, has been reported to be a potential antitumorigenic agent. This study aimed to investigate the mechanisms of action of HQ., Methods: Active ingredients and putative targets of HQ were obtained through a comprehensive search of the Traditional Chinese Medicine Systems Pharmacology database. CRC-related targets were retrieved from the GeneCards database and then overlapping targets were acquired. After visualization of the compound-disease network and protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping genes were performed. Additionally, HCT116 cells were treated with the active components of HQ at a 20-µM concentration. Cell Counting Kit-8 was used to detect cell activity, and real-time quantitative polymerase chain reaction was carried out to detect the expression of genes downstream of the interleukin (IL)-17 signaling pathway., Results: A PPI network comprising 177 nodes and 318 edges was obtained. The GO analysis of the overlapping genes showed enrichment in response to lipopolysaccharide and oxidative process. For the KEGG analysis, the AGE-RAGE signaling pathway and inflammation-related pathways, such as the IL-17 and tumor necrosis factor (TNF) signaling pathways, were enriched. The in vitro experiments showed that HQ promoted the apoptosis of CRC cells by inhibiting the expression of the CCL2, CXCL8, CXCL10, and PTGS2 genes., Conclusions: This study systematically revealed the multitarget mechanism of HQ in CRC through a network pharmacology approach. We verified that HQ promotes CRC cell death via the IL-17 signaling pathway. This finding provides indications for further mechanistic studies and the development of HQ as a potential treatment for CRC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-2596). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

On the cover: The cover image is based on the Research Article Developmental anatomy of anomalous structure and classification of commercial specifications and grades of the Astragalus membranaceus var. mongholicus by Renqing Li et al., DOI: https://doi.org/10.1002/jemt.23111. [ABSTRACT FROM AUTHOR]

The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi ( Radix Astragali ) and Huanglian ( Rhizoma Coptidis ) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.