Angelica sinensis (Oliv.) Diels, is a perennial herbaceous plant of the Umbelliferae family. It has a long history of cultivation and is highly valued as a traditional Chinese medicine in China (Zhang et al. 2012). In September 2023, leaf blight on A. sinensis with an average disease incidence of 56% was recorded in an approximately 6.7-ha production field in Lijiang, Yunnan province, China (26.8215°N, 100.2369°E). At first, small, chlorotic lesions appeared on the leaves. They subsequently increased in density and gradually merged, causing leaves to yellow and wither. Ultimately the blight casused death of the entire foliage. In order to identify the causal agent, cross-sectional segments (5×5 mm2) were cut from the edge of leaf lesions, surface disinfected with a 1% sodium hypochlorite solution for 3 min and rinsed three times with sterile distilled water. They were subsequently placed on potato dextrose agar (PDA) plates and incubated for 3 days under a 12-h photoperiod at 28℃. A total of ten isolates with similar morphological characteristics were obtained by single spore isolation. After 10 days of incubation on PDA, the colony morphology of these isolates was characterized by a brownish central area with a white edge. Aged colonies became wrinkled in the center of the colony. Conidia (n = 30) were elliptical and brown, with a size range of 4.11 to 6.55 μm (average 5.37±0.74 μm) × 3.17 to 4.62 μm (average 3.92±0.43 μm). Chlamydospores (n = 30) formed chains in series, spherical or elliptical in shape, ranging from yellow-brown to dark brown, with a size range of 12.30 to 13.70 μm (average 12.98±0.46 μm) × 4.20 to 5.30 μm (average 4.63±0.26 μm). The nuclear ribosomal internal transcribed spacer region (ITS), the second largest subunit of RNA polymerase II (RPB2), and the 28S nuclear ribosomal large subunit rRNA (LSU) region of two isolates were amplified with the primer pairs ITS1/ITS4 (White et al. 1990), fRPB2-5F/fRPB2-7cR (Liu et al. 1999), and LR0R/LR5 (Schoch et al. 2012), respectively. These amplicons were sequenced bidirectionally and assembled. The two isolates produced the same nucleotide sequences, and the sequences of a representative isolate (AsDp1) were deposited in GenBank. BLASTn analyses showed that the ITS (PP510616), RPB2 (PP526010), and LSU (PP550143) sequences of isolate AsDp1 were 100%, 99.66%, and 100% identical with those of Didymella pomorum ex-type isolate CBS 354.52 (MH857081, KT389616, and MH868616), respectively. A phylogenetic tree was constructed based on the ITS, RPB2, and LSU concatenated nucleotide sequences using the maximum likelihood method in MEGAX. Isolate AsDp1 was clustered with four D. pomorum isolates. According to the morphological and nucleotide sequences analyses, isolate AsDp1 was identified as D. pomorum (Chen et al. 2015). To determine pathogenicity, 1-year-old A. sinensis plants (approximately 20 cm tall) grown in 7-liter pots filled with sterilized field soil were sprayed until runoff with a 1×106 conidia/ml suspension of isolate AsDp1 onto the foliage, while control plants were sprayed with sterile water. All plants were cultivated under a 12-h photoperiod at 25℃. The pathogenicity tests were performed in triplicate with ten plants in each treatment. After fifteen days, numerous chlorotic lesions appeared on the leaves of all inoculated plants. The symptoms were similar to those found on naturally infected plants in the field, while the control plants remained asymptomatic. Subsequently, D. pomorum was reisolated from the diseased leaves, and the identity was confirmed based on its ITS sequence and morphological characteristics. D. pomorum causing stem canker on Rosa spp. was reported in Canada (Ilyukhin 2022). To our knowledge, this is the first report of D. pomorum causing leaf blight on A. sinensis in China. This etiological finding will potentially pave the way for the development of control strategies of this disease.

Angelica sinensis (AS) can improve the haematopoietic function, but the treatment mechanism is unknown. Transfusion dependency was estimated by Kaplan-Meier survival analyses and Cox proportional-hazard model in AS treated apalstic anemia (AA) patients. After that, the AA GEO database was analysed, the up differentially expressed genes (DEGs) of AA were combined with AS targets for the intersection of targets. After the AA mouse model was established, the effect of AS was confirmed by haematopoietic function tests. The same experiment plus mitochondrial apoptotic pathway tests in vivo were performed in Angelica sinensis polysaccharide (ASP)-treated mice, the key ingredient in AS. For in vitro experiment, bone marrow nucleated cells (BMNCs) were tested. Clinical data confirmed that the level of transfusion dependency and IL17A were lower in AS-users compared to non-AS users (p < 0.001). The intersection of targets between AA and AS most concentrated on inflammation and apoptosis. Then, the same effect was found in AS treated AA mice model. In both in vivo and in vitro tests, ASP demonstrated the ability to mitigate P38/MAPK-induced Bax-associated mitochondrial apoptosis, while also reducing the levels of activated Th17 cells and alleviating abnormal cytokine levels. So, the protective effect of AS and ASP on hematopoietic function lies in their ability to prevent apoptosis.

Angelica sinensis (Oliv.) Diels (AS) is a commonly used herbal medicine and culinary spice known for its gastrointestinal protective properties. Angelica sinensis oil (AO) is the main bioactive component of AS. However, the therapeutic effects and mechanisms of AO on the gastrointestinal tract remain unclear. In this study, we aim to investigated the potential of AO in restoring gut microbiota disorder and metabolic disruptions associated with ulcerative colitis (UC). A systematic chemical characterization of AO was conducted using GC×GC-Q TOF-MS. A UC mouse model was established by freely drinking DSS to assess the efficacy of AO. Utilizing 16 S rRNA sequencing in combination with untargeted metabolomics analysis of serum, we identified alterations in gut microbiota, differential metabolites, and pathways influenced by AO in UC treatment, thereby elucidating the therapeutic mechanism of AO in UC management. Pharmacodynamic results indicated that AO effectively inhibited the content of inflammation mediators, such as Interleukin-1β, Interleukin-6 and tumor necrosis factor-α, and proserved colon tissue integrity in UC mice. Furthermore, AO significantly downregulated the abundance of pathogenic bacteria (Bacteroidetes, Proteobacteria, and Desulfobacteriaceae) while increasing the abundance of beneficial bacteria (Firmicutes, Blautia, Akkermansia, and Lachnospiraceae). Metabolomics analysis highlighted significant disruptions in endogenous metabolism in UC mice, with a notable restoration of SphK1 and S1P levels following AO administration. Besides, we discovered that AO regulated the balance of sphingolipid metabolism and protected the intestinal barrier, potentially through the SphK1/MAPK signaling pathway. Overall, this study indicated that AO effectively ameliorates the clinical manifestations of UC by synergistically regulating gut microbe and metabolite homeostasis. AO emerges as a potential functional and therapeutic ingredient for UC treatment.

BACKGROUND: Angelica sinensis (AS) and Chuanxiong rhizoma (CR) are frequently prescribed in clinical settings for their ability to enrich blood, regulate menstrual cycles, and alleviate pain. Despite their widespread use, there is a relative dearth of studies exploring their anti-inflammatory properties.
OBJECTIVE: To evaluate the antioxidant and anti-inflammatory effects of Angelica sinensis-Chuanxiong rhizoma (ASCR) extracts and investigate its anti-inflammatory mechanisms.
METHODS: AS and CR were combined in six ratios and extracted using five solvents. The quality of the resulting ASCR extracts was assessed by determining the content of ferulic acid (FA) using HPLC. The antioxidant effects of the ASCR extracts were evaluated in vitro using the DPPH and ABTS assays, as well as in HUVECs exposed to H2O2-induced oxidative damage. Additionally, the anti-inflammatory effects of the extracts were investigated in vivo through the assays of ear edema in mice and paw edema in rats. Biochemical markers including NO, MDA, and SOD in paw tissues, as well as PGE2, TNF-α, and COX-2 in rat serum, were measured to further elucidate the anti-inflammatory mechanisms of ASCR extracts.
RESULTS: The WA-2-1 was obtained by combining AS and CR in a 2:1 ratio through first water then ethanol extraction, and showed favorable antioxidant and anti-inflammatory activities. The extract demonstrated effective scavenging abilities against DPPH• and ABTS+• radicals while also protecting against H2O2-induced oxidative damage. Furthermore, in vivo studies revealed that WA-2-1 had significant inhibitory effects on ear and paw edema as well as the ability to decrease NO and MDA levels, enhance SOD activity, and downregulate the expression of COX-2, PGE2, and TNF-α.
CONCLUSIONS: The combination of AS and CR exhibits favorable anti-inflammatory effects, attributed to its dual actions of mitigating oxidative stress and suppressing the production of inflammatory mediators in serum or tissues during the inflammatory process.

A new pair of butylphthalide diastereomers, dangguinolide A (1) and dangguinolide B (2), together with two known butylphthalide were isolated from Angelica sinensis. Their structures were determined by extensive spectroscopic analyses, and the absolute configurations of 1 and 2 were assigned via NMR calculations and ECD calculations. Their anti-inflammatory activities have evaluated in vitro.

Angelica sinensis is a long-standing medicine used by Chinese medical practitioners and well-known for its blood-tonic and blood-activating effects. Ferulic acid, ligustilide, and eugenol in Angelica sinensis activate the blood circulation; however, the material basis of their blood-tonic effects needs to be further investigated. In this study, five homogeneous Angelica sinensis polysaccharides were isolated, and their sugar content, molecular weight, monosaccharide composition, and infrared characteristics determined. Acetylphenylhydrazine (APH) and cyclophosphamide (CTX) were used as inducers to establish a blood deficiency model in mice, and organ indices, haematological and biochemical parameters were measured in mice. Results of in vivo hematopoietic activity showed that Angelica sinensis polysaccharide (APS) could elevate erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and interleukin-3 (IL-3) serum levels, reduce tumor necrosis factor-α (TNF-α) level in mice, and promote hematopoiesis in the body by regulating cytokine levels. Biological potency test results of the in vitro blood supplementation indicated strongest tonic activity for APS-H2O, and APS-0.4 has the weakest haemopoietic activity. The structures of APS-H2O and APS-0.4 were characterized, and the results showed that APS-H2O is an arabinogalactan glycan with a main chain consisting of α-1,3,5-Ara(f), α-1,5- Ara(f), β-1,4-Gal(p), and β-1,4-Gal(p)A, and two branched chains of β-t-Gal(p) and α-t-Glc(p) connected to each other in a (1→3) linkage to α-1,3,5-Ara(f) on the main chain. APS-0.4 is an acidic polysaccharide with galacturonic acid as the main chain, consisting of α-1,4-GalA, α-1,2-GalA, α-1,4-Gal, and β-1,4-Rha. In conclusion, APS-H2O can be used as a potential drug for blood replenishment in patients with blood deficiency, providing a basis for APS application in clinical treatment and health foods, as well as research and development of new polysaccharide-based drugs.

OBJECTIVE: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model.
METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed.
RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively).
CONCLUSIONS: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Myocardial fibrosis can induce cardiac dysfunction and remodeling. Great attention has been paid to traditional chinese medicine (TCM) \'s effectiveness in treating MF. Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract (RAS-RA), which is a key TCM compound preparation, have high efficacy in regulating inflammation. However, studies on its therapeutic effect on radiation-induced myocardial fibrosis (RIMF) are rare. In this study, RAS-RA had therapeutic efficacy in RIMF and elucidated its mechanism of action. First, we formulated the prediction network that described the relation of RAS-RA with RIMF according to data obtained in different databases. Then, we conducted functional enrichment to investigate the functions and pathways associated with potential RIMF targets for RAS-RA. In vivo experiments were also performed to verify these functions and pathways. Second, small animal ultrasound examinations, H&E staining, Masson staining, transmission electron microscopy, Enzyme-linked immunosorbent assay (ELISA), Western-blotting, Immunohistochemical method and biochemical assays were conducted to investigate the possible key anti-RIMF pathway in RAS-RA. In total, 440 targets were detected in those 21 effective components of RAS-RA; meanwhile, 1,646 RIMF-related disease targets were also discovered. After that, PPI network analysis was conducted to identify 20 key targets based on 215 overlap gene targets. As indicated by the gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis results, inflammation and PI3K/AKT/mTOR pathways might have important effects on the therapeutic effects on RIMF. Molecular docking analysis revealed high binding of effective components to targets (affinity < -6 kcal/mol). Based on experimental verification results, RAS-RA greatly mitigated myocardial fibrosis while recovering the cardiac activity of rats caused by X-rays. According to relevant protein expression profiles, the PI3K/AKT/mTOR pathway was important for anti-fibrosis effect of RAS-RA. Experimental studies showed that RAS-RA improved cardiac function, decreased pathological damage and collagen fiber deposition in cardiac tissues, and improved the mitochondrial structure of the heart of rats. RAS-RA also downregulated TNF-α, IL-6, and IL-1β levels. Additionally, RAS-RA improved the liver and kidney functions and pathological injury of rat kidney and liver tissues, enhanced liver and kidney functions, and protected the liver and kidneys. RAS-RA also increased PI3K, AKT and mTOR protein levels within cardiac tissues and downregulated α-SMA, Collagen I, and Collagen III. The findings of this study suggested that RAS-RA decreased RIMF by suppressing collagen deposition and inflammatory response by inhibiting the PI3K/AKT/mTOR pathway. Thus, RAS-RA was the potential therapeutic agent used to alleviate RIMF.

UNASSIGNED: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.
UNASSIGNED: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK-8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.
UNASSIGNED: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.
UNASSIGNED: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.

Breast cancer (BC) is one of the most common malignant tumors in women. Angelica sinensis polysaccharide (ASP) is one of the main components extracted from the traditional Chinese medicine Angelica sinensis. Research has shown that ASP affects the progression of various cancers by regulating miRNA expression. This study aimed to explore the specific molecular mechanism by which ASP regulates BC progression through miR-3187-3p. After the overexpression or knockdown of miR-3187-3p and PDCH10 in BC cells, the proliferation, migration, invasion, and phenotype of BC cells were evaluated after ASP treatment. Bioinformatics software was used to predict the target genes of miR-3187-3p, and luciferase gene reporter experiments reconfirmed the targeted binding relationship. Subcutaneous tumor formation experiments were conducted in nude mice after the injection of BC cells. Western blot and Ki-67 immunostaining were performed on the tumor tissues. The results indicate that ASP can significantly inhibit the proliferation, migration, and invasion of BC cells. ASP can inhibit the expression of miR-3187-3p in BC cells and upregulate the expression of PDCH10 by inhibiting miR-3187-3p. A regulatory relationship exists between miR-3187-3p and PDCH10. ASP can inhibit the expression of β-catenin and phosphorylated glycogen synthase kinase-3β (p-GSK-3β) proteins through miR-3187-3p/PDCH10 and prevent the occurrence of malignant biological behavior in BC. Overall, this study revealed the potential mechanism by which ASP inhibits the BC process. ASP mediates the Wnt/β-catenin signaling pathway by affecting the miR-3187-3p/PDCH10 molecular axis, thereby inhibiting the proliferation, migration, invasion, and other malignant biological behaviors of BC cells.