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.

UNASSIGNED

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.

Background: Luhong formula (LHF)-a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd-is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis.

<strong class="sub-title"> Methods: </strong> Forty-eight SD male rats were randomly assigned into six groups (<i>n</i> = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-<i>β</i>1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-<i>β</i>1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope.

<strong class="sub-title"> Results: </strong> LHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-<i>β</i>1, caspase-3, VEGF, and VEGFR2 expression.

<strong class="sub-title"> Conclusion: </strong> LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-<i>β</i>1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

This review attempts to collate existing data and provide the perspectives for future studies on the effects of plants on the male gonads. For many of these medicinal plants such as Lepidium meyenii, Rupus coreanus, Tribulus terrestres, Panax ginseng, Petasites japonicas, Apium graveolens, Eurycoma longifólia, Pedalium murex, Corchorus depressus, Mucuna pruriens, Astragalus membranaceus, Nigella sativa, Crataegus monogyna, Fagara tessmannii, Phaleria macrocarpa, Anacyclus pyrethrum, Cynomorium songaricum and Morinda officinalis, the mechanism of actions of their active principles and crude extracts has been shown in both laboratory animals, in vitro, and human studies, and includes their antioxidant, anti-inflammatory, spermatogenesis-inducing, aphrodisiac, smooth muscle relaxing and androgenic properties. Several active chemical leads including glucosinolates, anthocyanins, protodioscin, ginsenosides, sesquiterpenes, phyto-oestrogens, quassinoids, diosgenin, thymoquinone, proanthocyanidins and bajijiasu isolated from these plants are known to have target effects on the testis, but efforts have been limited in their application at the clinical level. There still appear to be many more extracts of medicinal plants that have not been characterised to determine the phytochemicals unique to them that have target effects on the gonads. Further, collaborative efforts at isolating pro-drug candidates from medicinal plants for studies at the molecular, cellular and clinical level towards elucidating their mechanisms of action on the testes are therefore warranted in the light of the current male fertility crisis.

The objectives of this study were to assess the effects of supplementation of Astragalus membranaceus root powder (AMP) and AMP processed to different particle sizes on growth performance, antioxidant status, and serum metabolites of broiler chickens. The experiment was conducted with one hundred twenty 1-d-old Arbor Acres broilers in 5 groups of 4 cages and for both starter (0 to 21 d) and grower (22 to 42 d) phases. The treatments were basal diet only (control) and basal diet supplemented with 5 g/kg of diet of AMP processed to particle sizes of 300, 149, 75, or 37 µm. Average daily gain, ADFI, and feed conversion rate (FCR) were determined weekly, and carcass yield, serum antioxidant enzyme activity, and metabolites were determined at 21 and 42 d of the experiment. Supplementation of AMP increased (P < 0.01) activities of total superoxide dismutase (TSOD) and glutathione peroxidase (GSHPx), but reduced (P < 0.01) concentrations of malondialdehyde (MDA) and cholesterol in the serum of chickens at 21 and 42 d. Reducing AMP particle sizes from 300 to 37 µm linearly increased (P < 0.01) TSOD and GSHPx activities at 21 and 42 d, but linearly decreased (P < 0.01) MDA at 42 d. Concentrations of total protein, albumin, and globulin in the serum were also increased (P < 0.05) or tended to be increased (P = 0.05 to 0.10) by AMP and linearly increased (P < 0.01) as the AMP particle sizes decreased. However, both treatments had no effect on ADG, ADFI, or FCR throughout the entire experiment period, although carcass yield increased (P < 0.05) at 42 d. Dietary supplementation of AMP at the concentration of 5 g/kg of diet enhanced serum antioxidant status and its efficacy linearly increased as the AMP particle size decreased from 300 to 37 µm, but had no effect on growth performance of broilers.

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

Objective: To analyse the clinical features of diabetic peripheral neuropathy (DPN) and employ data mining technology to explore the rules of Chinese herbal medicine (CHM) therapy.

Methods: The clinical data of 216 patients with DPN and qi-yin deficiency syndrome were obtained, and the clinical features of the patients were assessed by cluster analysis. Relevant information was entered into the clinical diagnosis and treatment collection system, and data mining techniques were used to analyse the drug frequency, core CHM, CHM pair, and so on.

Results: In this study, glycated haemoglobin (HbA1c) and homocysteine (HCY) were closely related to the pathogenesis of DPN. Overall, 162 patients had typical DPN syndrome characteristics, and we analysed 216 prescriptions, including 182 CHM. The frequencies of prescription of Astragalus membranaceus, Ligusticum wallichii, Poria cocos, and Radix Rehmanniae were greater than 45%. A Bayesian network analysis diagram showed that the 9 most common core CHM included Astragalus membranaceus, Ligusticum wallichii, Poria cocos, atractylodes rhizome, and Salvia miltiorrhiza Bge. According to the association rules of CHM, Radix Ophiopogon is used for Codonopsis pilosula; Astragalus membranaceus and atractylodes rhizome for Rehmannia are also frequently used. Astragalus membranaceus and Cinnamomi Ramulus or Ligusticum wallichii and Moutan bark were highly related to a decreased Michigan Diabetic Neuropathy Score.

Conclusion: HbA1c and HCY are related risk factors for DPN. Numbness is a typical syndrome characteristic. Astragalus membranaceus is a monarch CHM and is used most frequently.

Demyelination is the hallmark of multiple sclerosis (MS). Promoting remyelination is an important strategy to treat MS. Our previous study showed that Astragalus polysaccharides (APS), the main bioactive component of Astragalus membranaceus, could prevent demyelination in experimental autoimmune encephalomyelitis mice. To investigate the effects of APS on remyelination and the underlying mechanisms, in this study we set up a cuprizone-induced demyelination model in mice and treated them with APS. It was found that APS relieved the neurobehavioral dysfunctions caused by demyelination, and efficaciously facilitated remyelination in vivo. In order to determine whether the mechanism of enhancing remyelination was associated with the differentiation of neural stem cells (NSCs), biomarkers of NSCs, astrocytes, oligodendrocytes and neurons were measured in the corpus callosum tissues of mice through Real-time PCR, Western blot and immunohistochemistry assays. Data revealed that APS suppressed the stemness of NSCs, reduced the differentiation of NSCs into astrocytes, and promoted the differentiation into oligodendrocytes and neurons. This phenomenon was confirmed in the differentiation model of C17.2 NSCs cultured in vitro. Since Sonic hedgehog signaling pathway has been proven to be crucial to the differentiation of NSCs into oligodendrocytes, we examined expression levels of the key molecules in this pathway in vivo and in vitro, and eventually found APS activated this signaling pathway. Together, our results demonstrated that APS probably activated Sonic hedgehog signaling pathway first, then induced NSCs to differentiate into oligodendrocytes and promoted remyelination, which suggested that APS might be a potential candidate in treating MS.

Keywords: Astragalus polysaccharides; Sonic hedgehog signaling pathway; multiple sclerosis; neural stem cells; oligodendrocytes; remyelination.

Sanhuang mixture (Xinmai capsule) is composed of Astragalus membranaceus, Coptis chinensis and Scutellaria baicalensis. It could inhibit platelet aggregation (PAG) induced by ADP in rats or by ADP and ADR in vivo. Patients with high PAG took Xinmai capsule for 4 weeks, the effective rate was 88.7%, which was same as the efficacy of aspirin 50 mg/day. In Syndrome Differentiation of TCM, the effective rate was the highest (92.3%) in the Syndrome of Qi Deficiency-Blood Stasis, and the lowest (72.7%) in the Syndrome of Stasis Phlegm and combined together.

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.

Introduction: Calycosin (CA), a typical phytoestrogen extracted from root of Astragalus membranaceus. On the basis of summarizing the pharmacological and pharmacokinetic studies of CA in recent years, we hope to provide useful information for CA about treating different diseases and to make suggestions for future research. Areas covered: We collected relevant information (January 2014 to March 2020) on CA via the Internet database. Keywords searched includ pharmacology, pharmacokinetics and toxicology, and the number of effective references was 118. CA is a phytoestrogen with wide range of pharmacological activities. By affecting PI3K/Akt/mTOR, WDR7-7-GPR30, Rab27B-β-catenin-VEGF, etc. signaling pathway, CA showed the effect of anticancer, anti-inflammatory, anti-osteoporosis, neuroprotection, hepatoprotection, etc. Therefore, CA is prospective to be used in the treatment of many diseases. Expert opinion: Research shows that CA has a therapeutic effect on a variety of diseases. We think CA is a promising natural medicine. Therefore, we propose that the research directions of CA in the future include the following. Carrying out clinical research trials in order to find the most suitable medicinal concentration for different diseases; Exploring the synergistic mechanism of CA in combination with other drugs; Exploring ways to increase the blood circulation concentration of CA.

Keywords: Calycosin; anticancer; pharmacokinetics; pharmacology; traditional Chinese medicine.

Epithelial‑mesenchymal transition (EMT) serves an important role in tumor migration and invasion. Astragalus polysaccharide (APS), which is the main component of the traditional Chinese medicine Astragalus membranaceus, has been identified to display an antitumor effect. However, the effects and mechanisms of APS during breast cancer migration and invasion are not completely understood. The present study investigated whether APS inhibited breast cancer migration and invasion by modulating the EMT pathway. An MTT assay and a Ki67 immunofluorescence staining assay demonstrated that APS inhibited the proliferation of breast cancer cells. The results of the wound healing and Transwell Matrigel invasion assays suggested that APS decreased the migration and invasion of breast cancer cells. The western blotting and immunofluorescence analyses further demonstrated that APS had a regulatory effect on EMT‑related molecules. APS decreased the expression levels of Snail and vimentin, but increased E‑cadherin expression. APS also downregulated Wnt1, β‑catenin and downstream target expression. Additionally, the present results suggested that APS decreased the proliferation, and EMT‑mediated migration and invasion of cells by inhibiting the Wnt/β‑catenin signaling pathway. The present study suggested that APS may serve as a promising therapeutic agent for breast cancer.

Astragalus membranaceus (Radix Astragali, RA) and Atractylodes macrocephala (Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control media or media containing spermidine (5 μmol·L-1, SPD), alpha-difluoromethylornithine (2.5 mmol·L-1, DFMO), 4-Aminopyridine (40 μmol·L-1, 4-AP), the polysaccharide extracts of RA or RAM (50, 100, or 200 mg·L-1), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca2+ ([Ca2+]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca2+]cyt and accelerated migration of IEC-6 cells, compared with the controls (P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca2+]cyt, but also restored IEC-6 cell migration to control level (P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased (P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0 : 14.1 : 0.3 : 19.9 : 181.3 : 6.3 in RA and 1.0 : 4.3 : 0.1 : 5.7 : 2.8 : 2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.

Background: Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats.

Methods: Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n = 8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1β, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot.

Results: In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1β, and IL-18 expression and fibrosis indexes in the kidney of rats.

Conclusion: AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.

Mongolian medicine is an indispensable part in developing traditional Mongolian medicine. This study is aimed to provide a basis for the formulation of clinical and Mongolian medicinal materials standards by clarifying the original plant and species collation of Mongolia medicine of &quot;saradma&quot;. Mongolian herbal medicine, as an important part of Mongolian medicine, is needed to study the authentic Mongolian medicine, in order to exert the best therapeutic effect in the application. The Mongolian medicine of &quot;saradma&quot; is a kind of medicinal material for diuresis, reinforcing kidney, and eliminating edema, for which comes from the roots, stems, leaves, flowers, fruits, seeds and other parts of medicinal plant. The ancient books of Mongolian medicine are the most important reference the research of Mongolian medicine varieties. This review adopts the method of inductive comparison of ancient books in order to summarize the conclusion of Mongolian medicine of &quot;saradma&quot;. According to the investigations, Mongolian medicine of &quot;saradma&quot; type is mainly Leguminosae plant, Oxytropis latibracteata, Hedysarum multijugum, Thermopsis barbata, Astragalus membranaceus, Vicia amoena, O. caerulea, Astragalus bhotanensis, Hedysarum sikkimense. Compared with modern works, it is found that the drug has a wide range of resources distribution and application. It can be used for the treatment of cold edema, hot edema, nephrogenic edema, edema, swelling and likes caused by different diseases. Based on the research of Mongolian medicine of &quot;saradma&quot; varieties, it was found that the most commonly used varieties in Inner Mongolia were cayan saradma, xara saradam and sira saradma all of which are all top-grade drugs that reduce swelling.

Keywords: Mongolian medicine; saradma; variety textual research.

Purpose: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation.

Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot.

Results: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2.

Conclusion: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.

Keywords: Danggui Buxue Decoction; metastatic tumor; network pharmacology; perioperative period; primary tumor.

Introduction: Cancer is the second leading cause of death, and the burden of cancer continues to grow globally. Research on the efficacy of combined administration of herbal medicine and anticancer drugs is also increasing. SH003 is a new herbal medicine composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. SH003 alone up to 4800 mg daily was found to be safe. Preclinical studies have shown SH003 to have a synergistic effect with coadministration of anticancer drugs. This study aimed to determine the maximum tolerated dose of SH003 combined with docetaxel in patients with lung or breast cancer.

Methods: This is an open-label, dose-escalation study to evaluate the safety of SH003 combined with docetaxel. Patients with lung or breast cancer will be recruited. The participants will be divided into 3 groups based on SH003 daily dose (2400, 3600, and 4800 mg); the medication will be taken orally for 21 days. The traditional 3 + 3 design will be adopted for the dose escalation. Dose-limiting toxicities are defined as grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events. The highest dose at which no more than 1 of the 6 patients experience dose-limiting toxicity will be determined as the maximum tolerated dose of SH003 combined with docetaxel.

Discussion: This study investigates the safety of SH003 when combined with docetaxel. The results of this study will provide a safe dose range for conducting therapeutic exploratory trials.

Trial registrations: ClinicalTrials.gov NCT04360317.

BACKGROUND

Cancer is a major health problem worldwide and the leading cause of death in many countries. The number of patients with cancer and socioeconomic costs of cancer continues to increase. SH003 is a novel herbal medicine consisting of Astragalus membranaceus, Angelica gigas and Trichosanthes Kirilowii Maximowicz. Preclinical studies have shown that SH003 has therapeutic anticancer effects. The aim of this study is to determine the maximum tolerated dose of SH003 in patients with solid cancers.

UNASSIGNED

This study is an open-label, dose-escalation trial evaluating the safety and tolerability of SH003. The traditional 3+3 dose-escalation design will be implemented. Patients with solid cancers will be recruited. According to dose level, the patients will receive one to four tablets of SH003, three times a day for 3 weeks. Toxicity will be evaluated using common terminology criteria for adverse events (CTCAE). Dose-limiting toxicities are defined as grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose will be determined by the highest dose at which no more than one of six patients experiences dose-limiting toxicity.

UNASSIGNED

This study has been approved by the institutional review board of the Ajou University Hospital (reference AJIRB-MED-CT1-16-311). The results of this study will be disseminated through a scientific journal and a conference.

BACKGROUND

NCT03081819; Pre-results.

The complete nucleotide sequence of the Astragalus membranaceus (Fisch.) Bunge var. membranaceus chloroplast genome was reported and characterized in this study. The chloroplast genome is a circular molecule of 123623 bp that belongs to the inverted repeat-lacking clade (IRLC). It comprises 110 genes, including 76 protein-coding genes, four unique rRNAs and 30 tRNAs. Similar to the plastomes of A. membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P. K. Hsiao and other closely related species, rpl22 and rps16 are absent. The phylogenetic analysis of 67 proteins from 29 chloroplast genomes belonging to IRLC provided strong support for the non-monophyly of Galegeae. This genome has provided a wealth of information for distinguishing varieties of A. membranaceus.

Keywords: Astragalus membranaceus; plastid genome.

Huang-Qi (Astragali Radix) is an herbal tonic widely used in China and many other countries. It is derived from the roots of Astragalus membranaceus and A. membranaceus var. mongholicus and shows potent cardiovascular protective effects. In this article, we comprehensively reviewed 189 small molecules isolated from the two Astragalus species and discussed the interspecies chemical differences. Moreover, we summarized the pharmacological activities and mechanisms of action of Huang-Qi and its major bioactive compounds for the treatment of cardiovascular diseases. This review covers 171 references published between February 1983 and March 2020.

Keywords: Astragali Radix; Astragalus spp.; Huang-Qi; cardiovascular diseases; chemical constituents; herbal medicine.

Ethnopharmacological relevance: The combination of Astragalus membranaceus and Salvia miltiorrhiza (AS) is an effective prescription that is widely used to treat chronic kidney disease (CKD) clinically in traditional Chinese medicine. Our previous studies have shown that AS can alleviate early CKD through the "gut-kidney axis", but the regulatory role of AS in the "gut-kidney axis" in the middle and late stages of CKD caused by cyclosporin A-induced chronic nephrotoxicity (CICN) has remained unclear.

Aim of the study: To explore the protective effect of AS by regulating the intestinal flora to further control the miRNA-mRNA interaction profiles in CICN.

Materials and methods: Thirty-two mice were divided into four groups: Normal (N) (olive oil), Model (M) (CsA, 30 mg kg^-1 d^-1), AS (CsA + AS, 30 + 8.4 g kg^-1 d^-1) and FMT-AS (CsA + Faeces of AS group, 30 mg + 10 mL kg^-1 d^-1). The mice were treated for 6 weeks. Changes in renal function related metabolites were detected, pathological changes in the colon and kidney were observed, and 16S rDNA sequencing was performed on mouse faeces. In addition, miRNA and mRNA sequencing were performed on the kidney to construct differential expression (DE) profiles of the other 3 groups compared with group M. The target mRNAs among the DE miRNAs were then predicted, and an integrated analysis was performed with the DE mRNAs to annotate gene function by KEGG. DE miRNAs and DE mRNAs related to CICN in the overlapping top 20 KEGG pathways were screened and verified.

Results: Eight metabolites that could worsen renal function were increased in group M, accompanied by thickening of the glomerular basement membrane, vacuolar degeneration of renal tubules, and proliferation of collagen fibres, while AS and FMT-AS intervention amended these changes to varying degrees. Simultaneously, intestinal permeability increased, the abundance and diversity of the flora decreased, and the ratio of Firmicum to Bacteroides (F/B) increased in group M. The AS and FMT-AS treatments reversed the flora disorder and increased probiotics producing butyric acid and lactic acid, especially Akkermansia and Lactobacillus, which might regulate the 12 overlapping top 20 KEGG pathways, such as Butanoate metabolism, Tryptophan metabolism and several RF-related pathways, leading to the remission of renal metabolism. Finally, 15 DE miRNAs and 46 DE mRNAs were screened as the therapeutic targets, and the results coincided with the sequencing results.

Conclusion: AS could alleviate renal fibrosis and metabolism caused by CICN through the "gut-kidney axis". Probiotics such as Akkermansia and Lactobacillus were the primary driving factors, and the miRNA-mRNA interaction profiles, especially Butanoate metabolism and Tryptophan metabolism, may be an important subsequent response and regulatory mechanism.

Keywords: 16S rDNA sequencing; Astragalus membranaceus and Salvia miltiorrhiza; CsA-induced chronic nephrotoxicity; gut-kidney axis; miRNA-mRNA sequencing.

Improving angiogenic capacity under hypoxic conditions is essential for improving the survival of skin grafts, as they often lack the necessary blood supply. The stable expression levels of hypoxia‑inducible factor‑1α (HIF‑1α) in the nucleus directly affect the downstream vascular endothelial growth factor (VEGF) signaling pathway and regulate angiogenesis in a hypoxic environment. Astragaloside IV (AS‑IV), an active component isolated from Astragalus membranaceus, has multiple biological effects including antioxidant and anti‑diabetic effects, and the ability to provide protection from cardiovascular damage. However, the mechanisms underlying these effects have not previously been elucidated. The present study investigated whether AS‑IV promotes angiogenesis via affecting the balance between ubiquitination and small ubiquitin‑related modifier (SUMO) modification of HIF‑1α. The results demonstrated that persistent hypoxia induces changes in expression levels of HIF‑1α protein and significantly increases the proportion of dysplastic blood vessels. Further western blotting experiments showed that rapid attenuation and delayed compensation of SUMO1 activity is one of the reasons for the initial increase then decrease in HIF‑1α levels. SUMO1 overexpression stabilized the presence of HIF‑1α in the nucleus and decreased the extent of abnormal blood vessel morphology observed following hypoxia. AS‑IV induces vascular endothelial cells to continuously produce SUMO1, stabilizes the HIF‑1α/VEGF pathway and improves angiogenesis in hypoxic conditions. In summary, the present study confirmed that AS‑IV stimulates vascular endothelial cells to continuously resupply SUMO1, stabilizes the presence of HIF‑1α protein and improves angiogenesis in adverse hypoxic conditions, which may improve the success rate of flap graft surgery following trauma or burn.

Background The glucose intolerance developed during pregnancy is called gestational diabetes mellitus (GDM). GDM has become a severe risk for the health of both mother and baby. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus and has been reported to have anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. Methods C57BL/KsJ-Lepdb/+ female mice were used as GDM model. The mRNA levels of relative genes in this research were detected by qRT-PCR. The protein levels of relative genes were analyzed by western blot. Serum lipid level was measured by ILab Chemistry Analyzer 300 PLUS. Results Glucose, insulin, and lipid profile levels in GDM mice model were decreased by AS-IV treatment. AS-IV down-regulated the expression of inflammatory genes and up-regulated the expressions of antioxidant genes in GDM mice model. AS-IV treatment reduced cAMP accumulation in liver and reduced hepatic gluconeogenesis in GDM mice. Conclusion This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in mice model through the regulation of cAMP accumulation and hepatic gluconeogenesis.