This study aimed to investigate the influence of Astragalus membranaceus (AM), Adenophora triphylla (AT), and Ulmus pumila (UP) extracts on the quality traits, palatability, and storage stability of sous-vide (SV) cooked chicken breasts. Chicken breasts were marinated in AM, AT, or UP extracts for 1 h, and then consistently cooked at a constant temperature of 60°C for 2 h. SV cooked chicken breasts with the UP extract exhibited lower lightness and higher yellowness values on the surface region compared to those with the AM and AT extracts (p<0.05). The control and UP groups displayed a similar overall visual acceptability (p>0.05), although the UP group had lower color acceptability (p<0.01). The UP group also had higher flavor and lower off-flavor intensities compared to the control group (p<0.05), although similar scores were observed in tenderness attributes and juiciness among the groups (p>0.05). Owing to these results regarding overall sensory acceptability, samples from the UP group were more preferred by the trained panelists compared to samples from the control group (p<0.001). On 14 d of cold storage, all the groups with herbal medicinal extracts exhibited a lower concentration of thiobarbituric acid-reactive substances than the control group (p<0.05), and the AT and UP groups showed lower values compared to the AM group due to their higher flavonoid contents (p<0.001). Therefore, meat marination with herbal plant extracts before SV cooking can be effective for enhancing the overall quality of SV cooked chicken breast.

Keywords: chicken breasts; herbal medicinal extracts; quality characteristics; sous-vide cooking; storage stability.

Swainsonine is an Astragalus membranaceus extract. It is indole, alkaloid, and soluble in water. Its effect on rat cardiomyocytes apoptosis, and the mechanisms underlying that effect, were investigated by inducing apoptosis in H9c2 cells. This was detected by MTT assay, Annexin V-FITC/propidium iodide double staining and western blotting. Flow cytometry and fluorescence microscopy were used to confirm swainsonine's effect on mitochondrial membrane potential and levels of reactive oxygen species, while an ATP-dependent bioluminescence assay kit served to find the ATP contents. Assessment was also carried out for peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) expression levels as well as those of such apoptosis-associated proteins as Cytochrome c, Caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). Overall, indications were that swainsonine may have the potential to inhibit viability of cells, decrease expression of PGC-1α, induce mitochondrial dysfunction, upregulate Cytochrome c, Bax and Caspase-3, and downregulate Bcl-2. The suggestion would be that apoptosis may be induced through signalling pathways in H9c2 cells mediated by mitochondria.

In this work, the changes in isoflavone levels and the expression of genes involved in their biosynthesis were studied in two Astragalus by UPLC-MS and real-time PCR after 10 days of UV-B treatment (λmax = 313 nm, 804 J m-2 ). Isoflavones were significantly induced by UV-B irradiation. The influence might be activated by the regulation of these target genes. Our results indicate that (1) the resistance of Astragalus membranaceus might not be as good as Astragalus mongholicus in the enhanced UV-B radiation environment; (2) the enhanced accumulation of calycosin and calycosin-7-glucoside with UV-B treatment in roots of A. mongholicus might be derived from formononetin which is synthesized in the leaves; (3) the glycosylation process could be stimulated and activated by the enhanced UV-B radiation in both A. mongholicus and A. membranaceus. In other words, glycosylation of isoflavones might play a crucial role for two Astragalus plants in response to UV-B stress. Overall, this study offered a feasible elicitation strategy to understand the accumulation pattern of isoflavone in A. mongholicus and A. membranaceus, and also provided a reference for the changes in isoflavone levels of Astragalus in UV-B enhanced environment in the future.

Atherosclerosis is a major pathogenic driver of cardiovascular diseases. Foam cell formation plays a key role in atherogenesis, which is affected by lipid disorder and inflammation. Therefore, inhibition of foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from A. membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. In this study, we determined whether TFA could inhibit atherosclerosis and uncovered the underlying mechanism. In vivo, ApoE deficient mice were treated with TFA and high-fat diet for 16 weeks. Subsequently, atherosclerotic lesions, hepatic steatosis and associated genes expression in vitro and in vivo were determined. We found that TFA reduced atherosclerotic lesion size and enhanced plaque stability, which might be attributed to improved lipid disorder, reduced inflammation and decreased monocyte adhesion. Mechanistically, TFA inhibited hepatic steatosis via regulating the genes responsible for lipid metabolism, by which ameliorating the lipid disorder. Moreover, in macrophage, TFA reduced the expression of scavenger receptors such as CD36 and SRA; and promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced miR-33 expression and dampened NFκB activity, by which de-repressing ABCA1/G1 activity and inhibiting the inflammation. Collectively, TFA can attenuate atherosclerosis via dual suppression of miR-33 and NFκB pathway, and partially through inhibition of scavenger receptors in macrophage. In addition, TFA ameliorates the hepatic steatosis and lipid disorder, which in turn contributes to the amelioration of atherosclerosis, suggesting that TFA might be a novel therapeutic approach for inhibition of atherosclerosis and hepatic steatosis.

Keywords: Astragalus flavone; atherosclerosis; hepatic steatosis; inflammation; lipid disorder.

Muscle atrophy is a common complication in chronic kidney disease (CKD). Inflammation and myostatin play important roles in CKD muscle atrophy. Formononetin (FMN), which is a major bioactive isoflavone compound in Astragalus membranaceus, exerts anti-inflammatory effects and the promotion of myogenic differentiation. Our study is based on myostatin to explore the effects and mechanisms of FMN in relation to CKD muscle atrophy. In this study, CKD rats and tumour necrosis factor α (TNF-α)-induced C2C12 myotubes were used for in vivo and in vitro models of muscle atrophy. The results showed that FMN significantly improved the renal function, nutritional status and inflammatory markers in CKD rats. Values for bodyweight, weight of tibialis anterior and gastrocnemius muscles, and cross-sectional area (CSA) of skeletal muscles were significantly larger in the FMN treatment rats. Furthermore, FMN significantly suppressed the expressions of MuRF-1, MAFbx and myostatin in the muscles of CKD rats and the TNF-α-induced C2C12 myotubes. Importantly, FMN significantly increased the phosphorylation of PI3K, Akt, and FoxO3a and the expressions of the myogenic proliferation and differentiation markers, myogenic differentiation factor D (MyoD) and myogenin in muscles of CKD rats and the C2C12 myotubes. Similar results were observed in TNF-α-induced C2C12 myotubes transfected with myostatin-small interfering RNA (si-myostatin). Notably, myostatin overexpression plasmid (myostatin OE) abolished the effect of FMN on the phosphorylation of the PI3K/Akt/FoxO3a pathway and the expressions of MyoD and myogenin. Our findings suggest that FMN ameliorates muscle atrophy related to myostatin-mediated PI3K/Akt/FoxO3a pathway and satellite cell function.

Keywords: PI3K/Akt/FoxO3a; formononetin; inflammation; muscle atrophy; myostatin; satellite cell function.

Baicalein, an active ingredient separated from Astragalus membranaceus, has shown its anticancer ability in various cancers. However, its effect on nasopharyngeal carcinoma has not been explored yet. The present study aimed to investigate the effect of baicalein on the growth, proliferation, apoptosis, and cell cycle of human nasopharyngeal carcinoma cells, as well as transplanted nude mouse xenograft. The results showed that baicalein inhibited the growth and proliferation of CNE1 and CNE2 cells in a time- and concentration-dependent manner. It also caused a significant increase in the number of cells in the G₀/G₁ phase and a decrease in the G₂/M phase, thereby reducing the number of cells entering mitosis and inhibiting the proliferation of tumor cells. Baicalein also significantly induced apoptosis of CNE1 and CNE2 cells. Western blots showed that baicalein decreased the expression of Bcl-xl and Mcl-1 and increased the expression of Bax, Bad, and caspase 3, 8, and 9. In CNE1- and CNE2-transplanted tumors of mice, baicalein significantly inhibited tumor growth. In conclusion, baicalein could inhibit the growth and proliferation of human nasopharyngeal carcinoma cells, change their cell cycle, and induce apoptosis. Baicalein also effectively limits both CNE1- and CNE2-transplanted tumors in nude mice. Downregulation of Bcl-xl and Mcl-1 proteins and upregulation of Bax and Bad may be involved in the mechanism.

Background: The majority of pediatric oncology patients report use of complementary and alternative medicine. Some naturopathic doctors (NDs) provide supportive pediatric oncology care; however, little information exists to formally describe this clinical practice. A survey was conducted with members of the Oncology Association of Naturopathic Physicians (OncANP.org) to describe recommendations across four therapeutic domains: natural health products (NHPs), nutrition, physical medicine, and mental/emotional support. Results: We had 99 respondents with a wide variance of clinical experience and aptitude to treat children with cancer. Of the majority (52.5%) of respondents who choose not to treat these children, the three primary reasons for this are lack of public demand (45.1%), institutional or clinic restrictions (21.6%), and personal reasons/comfort (19.6%). The 10 most frequently considered NHPs by all NDs are fish-derived omega-3 fatty acid (83.3%), vitamin D (83.3%), probiotics (82.1%), melatonin (73.8%), vitamin C (72.6%), homeopathic Arnica (69.0%), turmeric/curcumin (67.9%), glutamine (66.7%), Astragalus membranaceus (64.3%), and Coriolus versicolor/PSK (polysaccharide K) extracts (61.9%). The top 5 nutritional recommendations are anti-inflammatory diets (77.9%), dairy restriction (66.2%), Mediterranean diet (66.2%), gluten restriction (61.8%), and ketogenic diet (57.4%). The top 5 physical modality interventions are exercise (94.1%), acupuncture (77.9%), acupressure (72.1%), craniosacral therapy (69.1%), and yoga (69.1%). The top 5 mental/emotional interventions are meditation (79.4%), art therapy (77.9%), mindfulness-based stress reduction (70.6%), music therapy (70.6%), and visualization therapy (67.6%). Conclusion: The results of our clinical practice survey highlight naturopathic interventions across four domains with a strong rationale for further inquiry in the care of children with cancer.

The separation and determination of eight flavonoids in the radix of Astragalus membranaceus (Fisch.) Bge var. mongholicus (Bge.) Hsiao was achieved by using micellar electrokinetic chromatography (MEKC) with a diode array detector (DAD). The influence of background electrolyte (BGE) concentrations and pH, surfactant concentrations, organic solvents, temperature, and voltage on the separate procedure was systematically investigated. The optimal resolution was obtained with a micellar phase consisting of 100 mM sodium cholate, 25 % (v/v) acetonitrile, 20 mM Na2B4O7, and 20 mM H3BO3 buffer at pH 9.2 by using a fused silica capillary at + 25 kV and 25 degrees C. A high reproducibility and good linearity ( R2>> 0.9978) were obtained over the concentration range tested. The relative standard deviations (R.S.D.s) from intra-day and inter-day precision for injection were less than 4.42 %. Six plant samples from different locations were then analyzed for the flavonoids by this newly developed MEKC method.

Nowadays featuring outstanding eco-friendliness, the phytochemical fabrication method of nanostructures is very popular. Here, we propose to utilize the Astragalus membranaceus extract as the reducing and capping agent to stabilize the metal and to avoid the aggregations of nanoparticles during ZnO nanoflowers synthesis procedure. As a result, the whole fabrication procedure was highly efficient and cost-effective without requiring a special environment of high pressure or elevated temperature and without chemical hazards used or produced. After the fabrication, detailed characterization about material morphology and crystal structure was carried out, including scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscope (FTIR). Moreover, the ZnO nanoflowers demonstrated distinctive antibacterial, antioxidant and electrochemical sensing effect. Specifically, ZnO nanoflowers had an antibacterial inhibition zone of 19(±0.7) and 15(±0.8) mm in diameter against the concentration of 50 μL (1 mg/mL) Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which is greatly improved compared to the reference drug (Kanamycin). Besides, antioxidant activity was also tested using H₂O₂ free radical scavenging assay and 60% 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition of 0.5 mg/mL was reported. Finally, controlled by the diffusion process during the charge transfer procedure, 4-nitorphenol was dramatically reduced and a limit of detection of 0.08 μM by ZnO nanoflowers modified electrode was observed during the cyclic voltammetry (CV) experiment. Because the phenolic compounds originating from Astragalus membranaceus helped to facilitate the electron transfer, the limit of detection was lower compared to other materials, such as copper oxide nanoparticles (Cu₂O-NPs), silicon dioxide/silver nanoparticles (SiO₂/Ag-NPs), zinc oxide nanoparticles (ZnO-NPs), activated carbon (AC) and cobalt oxide nanocubes (Co₃O₄). Therefore, featuring easy operation, low-cost and eco-friendliness, our proposed ZnO nanoflowers fabrication method will have a great potential in biomedical and electro-catalytic fields.

Keywords: Antibacterial activity; Antioxidant activity; Astragalus membranaceus; Cyclic voltammetry; ZnO nanoflowers.

Objective: Astragaloside IV (AS IV) is antioxidant and anti-inflammatory product, which is extracted from the Chinese herb Astragalus membranaceus. It is widely used in a variety of inflammatory diseases. The research was to explored the protective effects of AS IV against lung injury induced by particulate matter 2.5 (PM2.5) in vivo.

Subjects and methods: Thirty-five male Sprague-Dawley rats were randomly divided into five groups (n=7 per group). (1) Normal saline group (NS), (2) AS IV group (AS) (100 mg/kg), (3) PM2.5 group (PM2.5), (4) PM2.5 + AS IV group (ASL) (50 mg/kg), and (5) PM2.5 + AS IVgroup (ASH) (100 mg/kg). Rats were pre-treated with AS IV intraperitoneally (50 and 100 mg/kg/day) for three days. Then, PM2.5 (7.5 mg/kg) was given by intratracheal instillation to induce lung injury. Six hours after PM2.5 stimulation, the rats were euthanized. Bronchoalveolar lavage fluid (BALF) was collected for assay of cytokines. Lung tissue was collected for oxidative stress, histology, immunohistochemistry, transmission electron microscope, and western blot analyses.

Results: AS IV alleviated PM2.5-induced lung injury by decreasing lung dry-wet ratio, reducing the level of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) in BALF, and reduced oxidative stress response in lung tissue. Western blot results revealed that AS-IV regulated the expression of TLR4/MyD88/NF-κB pathway proteins in lung tissues.

Conclusion: AS IV mitigated PM2.5 induced lung injury by regulating the activity of TLR4/MyD88/NF-κB signalling pathway, reducing inflammatory and oxidative stress responses.

Keywords: Astragaloside IV; Lung injury; PM2.5; TLR4/MyD88/NF-κB signalling pathway.

Background: Cisplatin is an effective chemotherapeutic drug for treating various cancers including non-small cell lung cancer (NSCLC), but resistance to cisplatin remains the main limitation to its use in clinic. Astragaloside IV (AS-IV), which is derived from Astragalus membranaceus, has been proven to participate in various anti-cancer activities including anti-cancer, anti-oxidative, and anti-inflammatory functions.

Method: In this study, we explored the role of AS-IV in cisplatin chemoresistance to NSCLC cells by establishing cisplatin-resistant the NSCLC cell lines, A549^Cis and H1299^Cis.

Results: Cisplatin inhibited viability and promoted apoptosis of A549^Cis and H1299^Cis cells in a dose-dependent manner. In addition, cisplatin upregulated the levels of autophagy-related proteins (Beclin1, LC3 II/I) and endoplasmic reticulum (ER) stress-related proteins (glucose regulated protein 78: GRP78, protein kinase R (PKR)-like endoplasmic reticulum kinase: PERK), indicating that cisplatin caused autophagy and ER stress in NSCLC cells. However, treatment combined with AS-IV dose-dependently suppressed cell viability and increased the cell apoptosis rate in A549^Cis and H1299^Cis cells, suggesting that AS-IV elevated the anti-tumor role of cisplatin in NSCLC cells. AS-IV treatment suppressed the expression of GRP78 and Beclin1. Inhibition of ER stress or autophagy both counteracted the inhibitory effect of AS-IV on chemoresistance to cisplatin in NSCLC cells.

Conclusions: AS-IV sensitized NSCLC cells to cisplatin through suppressing ER stress and autophagy. This study provides a novel strategy of cisplatin combined with AS-IV for the treatment of cisplatin-resistant NSCLC patients.

Keywords: Astragaloside IV (AS-IV); autophagy; cisplatin; endoplasmic reticulum stress (ER stress); non-small cell lung cancer (NSCLC).

Asthma is a chronic inflammatory lung disease of the airway; the incidence and prevalence of asthma remain high worldwide. Astragaloside IV (AS-IV) is the main active constituent of Astragalus membranaceus. Accumulating evidence suggests that AS-IV possesses anti-inflammatory and anti-asthmatic ability, but the potential molecular mechanism is required to further clarify. In this study, the anti-asthmatic effects of AS-IV on mice with ovalbumin (OVA)-induced allergic inflammation were analysed. We analysed airway hyperresponsiveness (AHR), numbers of inflammatory cells, inflammation situation in lung tissue and cytokines level in bronchoalveolar lavage fluid (BALF) between OVA-induced mice with and without AS-IV treatment. Moreover, we explored the possible signalling pathway behind the anti-asthmatic effects. Our results revealed that AS-IV treatment ameliorates airway inflammation and AHR in an OVA-induced asthma model. Besides, AS-IV treatment inhibits the interleukin (IL)-4, -5 and -13 production, and further study indicated that AS-IV treatment downregulates the expression level of p-JAK2/p-STAT6 proteins. Taken together, the present study suggested that the inhibitory effects of AS-IV on asthma therapy are at least partially involved in inhibiting the JAK2/STAT6 signalling pathway.

Decreased chemosensitivity among tumor cells is often an obstacle in cisplatin (Cis) chemotherapy. Overexpression of multidrug resistance-associated protein 2 (MRP2) is a key mechanism underlying decreased Cis chemosensitivity and resistance. Astragaloside IV (AS IV) is an important component derived from the well-known traditional Chinese herb Astragalus membranaceus. The aim of this study was to explore the role of AS IV in enhancing the antitumor effect of Cis by suppressing MRP2 expression in HepG2 cells and H22 tumor-bearing mice. After co-treatment of HepG2 cells with Cis and AS IV, we assessed the effects on cell proliferation and apoptosis. Tumor growth and apoptosis assessment were performed to assess chemosensitivity in H22 tumor-bearing mice. We used western blotting, immunofluorescence assays, and immunohistochemistry assays to detect MRP2 expression in HepG2 cells, H22 tumor tissues and mouse kidney tissues. AS IV enhanced Cis chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth in vitro and in vivo. MRP2 overexpression in tumor cells was induced by Cis, which contributes to decreased chemosensitivity and Cis resistance. Co-administration of AS IV suppressed MRP2 expression in tumor tissues, which might be an important mechanism for enhancing Cis chemosensitivity in hepatocellular carcinoma. Moreover, AS IV alleviated Cis-induced kidney injury in mice without changing MRP2 expression. In total, AS IV enhanced the antitumor effect of Cis against hepatocellular carcinoma by suppressing MRP2 expression in tumor cells. The results provide a new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.

The tumor prescriptions contained in Dictionary of Tumor Formulas, Compendium of Good Tumor Formulas, Chinese Pharmacopoeia, Ministry of Health Drug Standards for Chinese Medicine Formulas and National Compilation of Standards for Proprietary Chinese Medicines were selected and organized to construct a database for tumor prescriptions, and the data mining techniques were applied to investigate the prescription regularity of colorectal cancer prescriptions. The formula data were extracted after screening in strict accordance with the inclusion and exclusion criteria, and were then analyzed with Microsoft Excel 2010 for frequency statistics, Apriori block provided by SPSS Clementine 12.0 software for correlation rule analysis, and arules and arulesViz packages in R 4.0.2 software for correlation rule visualization. In addition, SPSS 18.0 software was used for cluster analysis and factor analysis, in which cluster analysis was performed by Ochiai algorithm with bicategorical variables in systematic clustering method and factor analysis was performed mainly with principal component analysis. A total of 285 prescriptions were included in the statistical analysis, and the frequency statistics showed that 43 herbs had been used more than 16 times. The association rules analysis showed that 26 high-frequency me-dicine pair rules were obtained, and the association rules for those dispelling evil spirits, strengthening the body, resolving stasis, dispelling dampness, etc. were visualized. In the cluster analysis, we generated a dendrogram from which 7 groups of traditional Chinese medicines with homogeneity were extracted. 10 common factors were obtained in the factor analysis. The types of herbal medicines involved in the colorectal cancer prescription included anti-cancer antidotes, strengthening and tonifying medicines, blood-regulating medicines, and expectorant medicines, corresponding to the treatment for eliminating evil spirits, strengthening, resolving stasis, and expectorating dampness. The prescriptions for anti-cancer detoxification were normally based on the pairs composed of Scutellaria barbata-Hedyotis diffusa and Sophora flavescens, Sargentodoxa cuneata, S. barbata, often combined with stasis relieving drug and dampness eliminating drug, reflecting the characteristics of treatment for both toxicity and stasis, dampness and toxicity simultaneously. The prescriptions for strengthening the righteousness and tonifying the deficiency were composed of Astragalus membranaceus and Atractylodes macrocephala mainly, exerting the effect of benefiting Qi, strengthening the spleen and drying dampness, tonifying kidney and essence, tonifying blood and invigorating blood. Meanwhile, anti-cancer detoxification medicines shall be reduced as much as possible. The compatibility of the medicines for the intestinal tract reflected the principle of using the right medicine for the right condition and eliminating evil spirits or strengthening the body, as appropriate.

Keywords: colorectal cancer; data mining; medication regularity; traditional Chinese medicine.

Astragaloside IV (AS-IV), a natural product derived from Radix Astragali (Astragalus membranaceus), is beneficial for the treatment of Alzheimer's disease (AD), but the mechanisms underlying this benefit are not completely understood. Peroxisome proliferator-activated receptor gamma (PPARγ) and brain-derived neurotrophic factor (BDNF) are potential therapeutic targets for AD. In this study, we found that amyloid β protein fragment 1-42 oligomers (AβO) suppressed BDNF and PPARγ expression, and inhibited tyrosine receptor kinase B (TrkB) phosphorylation in cultured hippocampal neurons; these changes were ameliorated by treatment with AS-IV. Inhibition of PPARγ by genetic and pharmacological methods also blocked the effect of AS-IV on BDNF expression in AβO-treated cells. Importantly, exogenous BDNF protected against neurotoxicity and apoptosis induced by AβO, whereas inhibition of PPARγ reversed protective effects of AS-IV against these outcomes. In vivo data further revealed that AS-IV improved AβO-induced memory impairment and reduced apoptosis of hippocampal neurons. Moreover, AS-IV suppressed the AβO-induced reduction in BDNF by promoting PPARγ activation in the hippocampus. Taken together, these results indicate that AS-IV prevents AβO-induced memory impairment and hippocampal neuronal apoptosis, probably by promoting the PPARγ/BDNF signaling pathway.

Keywords: Alzheimer’s disease; BDNF; PPARγ; amyloid beta; astragaloside IV.

Astragalus membranaceus (Astragalus) is often used as a medical and food resource in China. The present study was designed to investigate the features and effects of polysaccharide from Astragalus membranaceus (WAP) on rats with antibiotic-associated diarrhea (AAD). WAP was mainly composed of glucose, galactose, arabinose and glacturonic acid, with glucan, arabinogalactan and RG-I regions, and it showed loosely irregular sheet conformation. WAP decreased the inflammatory cell infiltration of colon in AAD rats, increased propionate and butyrate production, improved metabolic levels, adjusted the diversity and composition of gut microbiota, increased the relative abundance of Pseudomonas, and decreased the relative abundance of Allobaculum and Coprococcus. In conclusion, WAP contained different types of polysaccharide regions and sheet three-dimensional conformation, while it ameliorated AAD by recovering the colon structure, adjusting the gut microbiota, and improving the SCFAs levels. The results can provide some data basis for natural products to alleviate the side effects related to antibiotics.

Trace element contamination in Chinese herbal medicines has been recognized as a potential health concern for consumers. To assess the health risk to the herb-consuming population, nine trace elements (Cu, Cd, Cr, Mo, Ni, Pb, Sr, Zn, and As) were investigated based on their concentrations in three common medicinal plants (Astragalus membranaceus, Codonopsis tangshen, and Paris polyphylla var. chinensis) and soils from unpolluted and polluted areas in the Sichuan Province, China. The results showed that the metal content differed significantly in medicinal plants and soils from unpolluted versus polluted areas. No significant differences in metal accumulation were observed for these CHMs grown in either unpolluted or polluted areas. Evaluation of the health risk index suggested that soil ingestion and medicated diet represented the dominant exposure routes, indicating that trace metal(loids) in local soil might pose potential risks through soil-food chain transfer. Hazard quotient values for AM (1.473) and CT (1.357) were higher than the standard value (HQ > 1), whereas the hazard indices for PC, AM, and CT were 13.18, 14.33, and 14.01 times higher than the safe limit (HI > 1) in the polluted area, indicating non-cancer-related health hazards. Ingestion of soil was responsible for 36.39 to 91.06% of the total cancer risk and medicated diet accounted for 6.35 to 62.71%, compared with inhalation and dermal contact, suggesting carcinogenic health risks in herbs from polluted soils. In this study, Pb showed relatively higher non-carcinogenic risks, while Cr and Ni posed the highest cancer risks. Therefore, we propose more effective measures, which should be considered for Cr, Ni, and Pb remediation in soil to reduce their pollution in the studied areas.

Keywords: Cancer risk; Medicinal herb; Multi-medium exposure; Non-carcinogenic risk; Trace element contamination.

Homeostasis is a crucial concept used to describe the condition of patients and the roles of herbs in traditional Chinese medicine. Qi-deficiency pattern is one of the conditions when loss of homeostasis and is usually characterized by symptoms including lassitude, spontaneous sweating, and a weak pulse, which are not easy to quantitate. Codonopsis pilosula and Astragalus membranaceus were usually prescribed for carriers with hepatitis and patients with metastatic colon cancer, because these patients tended to experience fatigue. However, crude drugs were prescribed based on the exterior symptoms of patients without controlling clinical setting, such as gender, age, and dietary habits. Limited molecular evidence of using gene expression as the guide for description is available. Therefore, the purpose of this study was to identify potential and objective biomarkers of these two qi-related drugs in a simplified cellular system.

Aqueous extracts of crude qi-tonifying herbs, C. pilosula and A. membranaceus, and that of a qi-consuming drug, Citrus reticulata, were prepared. Human liver cancer HepG2 cells were treated with the extracts of qi-tonifying herbs for 24 h. Differentially expressed genes were identified using microarrays and quantitative RT-PCR (qRT-PCR) and validated in two other hepatocellular cell lines, Huh7 and L-02.

A total of 67 differentially expressed probes that responded to both herbs were identified. A pathway analysis revealed that these genes were involved in the development, growth, movement, and viability of the liver cells.

Conclusions

After qRT-PCR validation and examination of clinical data from public domains, our results showed that two genes, GDF15 and HMOX1, could serve as biomarkers in liver cells for identifying responses after treatment with C. pilosula and A. membranaceus.

Astragalus membranaceus is an important traditional Chinese herb whose roots have been used for medicinal purposes for more than 2000 years. Because of excessive exploitation, the wild resources are currently almost exhausted, and therefore, artificial planting of Astragalus membranaceus has been increasingly important. But to date, few studies have focused on the active ingredients and mineral element of Astragalus membranaceus in the Qinghai-Tibet Plateau.In this study, five density gradients (M1: 10 cm × 25 cm, M2: 15 cm × 25 cm, M3: 20 cm × 25 cm, M4: 25 cm × 25 cm and M5: 30 cm × 25 cm) were assessed to evaluate the effects of various planting densities on the mineral element and secondary metabolite content of Astragalus membranaceus roots in different months. It was found that the content of calycosin-7-O-β-D-glucoside and astragaloside IV reached its highest in October. Ononin content increased month by month, while formononetin content decreased during months. Calycosin content did not show significant changes during seasons. Taken together, these results suggest that the optimal planting density is 15 cm × 25 cm (D2) and the optimal harvest period is October. According to the results, the Cu content in all samples did not exceed the limit (20 mg/kg). Principal component analysis (PCA) revealed that Na, P, K Al, Ba, Ca, Fe, Li, and Mn were selected as characteristic elements of Astragalus membranaceus. The results also showed a high correlation between elements and active ingredients. Ba and Co had extremely significant associations with astragaloside IV.

Keywords: Active ingredients; Astragalus membranaceus; Mineral elements; Qinghai-Tibet Plateau; Seasonal change.

BACKGROUND

Astragalus extract mixture HT042 is a combination of three standardized extracts from Astragalus membranaceus root, Eleutherococcus senticosus stem, and Phlomis umbrosa root, which has proven to stimulate children's height growth.

OBJECTIVE

The aim of this study was to demonstrate the safety of HT042 and its three constituent herbs when administered orally.

METHODS

Acute and sub-chronic oral toxicity studies were conducted using male and female Sprague-Dawley rats. In the acute toxicity study, HT042 and each of the herbs was administered at single doses of up to 5000 mg/kg. In the 13-week sub-chronic toxicity study, HT042 was administered at repeated doses of up to 4000 mg/kg/day.

RESULTS

In the acute toxicity study of HT042 and each of the herbs, no deaths occurred and there was no indication of toxicity, on the basis of clinical signs, body weight, and necropsy findings. In the sub-chronic toxicity study of HT042, there were no deaths and no changes in clinical signs or the findings of ophthalmic examinations. Although there were some treatment-related changes in other findings, these alterations were not considered toxicologically significant because they remained within normal ranges or recovered during the recovery period.

CONCLUSIONS

The oral approximate lethal doses of HT042 and each of the herbs were>> 5000 mg/kg, and the no-observed-adverse-effect level of HT042 was 4000 mg/kg/day in male and female rats.

In this work, a water-soluble Astragalus membranaceus polysaccharide (AMP) was prepared by hot water extraction, and the effects of AMP on the serum cytokine levels and spermatogenesis of Kunming mice were investigated. Sixty Kunming mice were randomly divided into five groups: a normal control group, a model control group (treated with cyclophosphamide) and three treatment groups (treated with cyclophosphamide and 25, 50 and 75 mg/kg AMP). The effects of AMP on the serum cytokine levels and spermatogenesis of mice were evaluated. Intragastric treatment with different levels of AMP significantly increased serum interleukin-11, tumour necrosis factor-α and interferon-γ levels; protein expression and superoxide dismutase activity in testis; and sperm density, sperm movement and the rate of normal sperm morphology. In addition, AMP decreased the nitrate nitrogen level in the testes of Kunming mice compared with the model control group. The results indicated that AMP can ameliorate the immunity and spermatogenesis of mice with reproduction system impaired by cyclophosphamide.