Background: Cordyceps sinensis is a traditional Chinese medicine that has shown promise for the management of chronic bronchitis (CB). We aim to assess the efficacy and safety of a preparation of C sinensis named Bailing capsule (Hirsutella sinensis, Cs-C-Q80) compared with a placebo in patients with CB. Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial (Chinese Clinical Trial Registry; registration number: ChiCTR1900025707) recruited patients with CB from eight hospitals in China between May 2019 and December 2020. Patients were randomized 2:1 to receive Bailing capsule or a placebo orally for 48 weeks (2.0 g, three times a day). Results: Among 240 patients who were randomized, 238 (Bailing capsule: 159, placebo: 79) were included in the primary analysis. Bailing capsule significantly reduced the frequency of acute exacerbation of CB (AECB) compared with the placebo during treatment (0.43 ± 0.82 vs. 1.56 ± 1.34; P < 0.001) and follow-up (0.21 ± 0.64 vs. 0.45 ± 0.93; P = 0.026). Bailing capsule improved the severity of expectoration (P = 0.046) and wheezing (P = 0.010) in AECB during follow-up. The severity of CB after treatment was significantly improved in the Bailing capsule group compared with the placebo group (P = 0.035), particularly in terms of expectoration (P = 0.012) and wheezing (P = 0.003). The risk of adverse events, mainly including infectious and invasive diseases and gastrointestinal symptoms, did not significantly differ between the two groups (29.6% vs. 30.4%). Conclusion: In patients with CB, Bailing capsule significantly reduces the frequency of AECB and ameliorates the severity of AECB and CB symptoms. Clinical Trail Registration: https://www.chictr.org.cn, identifer ChiCTR1900025707.

Cordyceps sinensis, a traditionally prized medicinal fungus, contains polysaccharides as one of its main bioactive constituents, known for their significant immunomodulatory properties. In this study, we systematically investigated the composition and structure of Cordyceps sinensis polysaccharide, followed by an evaluation of its therapeutic effect on depression using a chronic restraint stress-induced depression model. The polysaccharide CSWP-2, extracted via hot water, precipitated with ethanol, and purified using DEAE-cellulose column chromatography from Cordyceps sinensis, is primarily composed of glucose, mannose, and galactose, with α-1,4-D-glucan as its major structural component. Behavioral tests, immunological profiling, metabolomics, and gut microbiota analyses indicated a notable ameliorative effect of CSWP-2 on depressive-like symptoms in mice. Furthermore, the action of CSWP-2 may be attributed to the modulation of the gut microbiome\'s abundance and its metabolic impacts, thereby transmitting signals to the host immune system and exerting immunomodulatory activity, ultimately contributing to its antidepressant effects.

Cordyceps sinensis is a rare and endangered medicinal herb in China and a typical medicinal and food plant. Most of the research related to Cordyceps sinensis focuses on its pharmacological effects, artificial cultivation and clinical applications. However, there are few comprehensive evaluations on the quality of Cordyceps sinensis under different drying methods. In this study, the effects of vacuum freeze-drying (DG), oven-drying (HG) and air-drying (YG) on the morphological characteristics, microstructure, antioxidant activity and metabolites of Cordyceps sinensis were investigated using wild Cordyceps sinensis as the research object. The results showed that in their appearance and morphology, the YG- and HG-method Cordyceps sinensis samples were darker in color and wilted, while the DG- method Cordyceps sinensis samples were golden yellow in color and had better fullness. In terms of microstructure, the stomata of the YG and HG method Cordyceps sinensis samples were relatively small and irregularly shaped, whereas those of the DG method Cordyceps sinensis samples were larger and neat. In terms of antioxidant capacity, the HG-method samples were the lowest, followed by the YG group, and the DG group had the highest total antioxidant capacity. A correlation analysis revealed a significant relationship between antioxidant capacity and lipids, lipid molecules, nucleosides, nucleotides, and analogs. A metabolomics analysis identified 1937 metabolites from 18 superclasses, with lipids, lipid-like molecules, organic acids and derivatives, organoheterocyclic compounds, and organic oxygen compounds being the predominant metabolites in Cordyceps sinensis. Differentially accumulated metabolites (DAMs) in DG samples showed higher levels of lipids and lipid molecules, organic oxygen compounds, organic acids and derivatives, and organoheterocyclic compounds compared to the other drying methods, suggesting DG as the optimal preservation method for Cordyceps sinensis. These findings offer insights for selecting appropriate drying methods and maintaining the post-drying quality of Cordyceps sinensis.

Cordyceps sinensis (C. sinensis) and Gymnema inodorum (Lour.) Decne. (G. inodorum) have been widely used for treating various illnesses. The study focused on exploring the effects of C. sinensis extract (CSE), G. inodorum extract (GIE), using alone and combined (COM) on ameliorating glucose intolerance, dyslipidemia, and obesity in mice fed with a high-fat diet (HFD). The results revealed that the oral glucose tolerance test (OGTT), total cholesterol (TC), triglycerides (TG), and LDL-cholesterol (LDL) exhibited a significant decrease in all groups treated with CSE, GIE, and COM compared to the control (p < 0.05). Obviously, CSE plus GIE exhibited a synergistic effect on amelioration of OGTT, TC, TG, and LDL, which is also the first report. Furthermore, the extracts showed no toxicity in the mice\'s vital organs. These results suggest that CSE, GIE, and their combined could have the potential as complementary therapeutic approaches for managing hyperglycaemia and dyslipidemia.

Cordyceps sinensis is a precious medicinal and edible fungus, which is widely used in body health care and disease prevention. The current research focuses on the comparison of metabolite characteristics between a small number of samples and lacks a comprehensive evaluation of the quality of C. sinensis in a large-scale space. In this study, LC-MS/MS, principal component analysis (PCA), hierarchical cluster analysis (HCA), and the membership function method were used to comprehensively evaluate the characteristics and quality of metabolites in 15 main producing areas of C. sinensis in China. The results showed that a total of 130 categories, 14 supercategories, and 1718 metabolites were identified. Carboxylic acids and derivatives, fatty acyls, organo-oxygen compounds, benzene and substituted derivatives, prenol lipids, and glycerophospholipids were the main components of C. sinensis. The HCA analysis and KEGG pathway enrichment analysis of 559 differentially accumulated metabolites (DAMs) showed that the accumulation models of fatty acids and conjugates and carbohydrates and carbohydrate conjugates in glycerophospholipid metabolism and arginine and proline metabolism may be one of the reasons for the quality differences in C. sinensis in different producing areas. In addition, a total of 18 biomarkers were identified and validated, which had a significant discrimination effect on the samples (p < 0.05). Overall, YS, BR, and ZD, with the highest membership function values, are rich and balanced in nutrients. They are excellent raw materials for the development of functional foods and provide scientific guidance for consumers to nourish health care.

The Bailing Capsule is a commonly used traditional Chinese medicine for the treatment of chronic kidney disease (CKD). However, its therapeutic effects and pharmacological mechanisms have not been fully explored. In this study, we integrated meta-analysis and network pharmacology to provide scientific evidence for the efficacy and pharmacological mechanism of Bailing Capsule in treating CKD. We conducted searches for randomized controlled studies matching the topic in PubMed, the Cochrane Library, Embase, Web of Science, and the Wanfang Database, and screened them according to predefined inclusion and exclusion criteria. Dates from the included studies were extracted for meta-analysis, including renal function indicators, such as 24-h urinary protein (24UP), blood urea nitrogen (BUN), and serum creatinine (Scr), as well as inflammatory indicators like high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Network pharmacology was employed to extract biological information, including active drug ingredients and potential targets of the drugs and diseases, for network construction and gene enrichment. Our findings indicated that 24UP, BUN, and Scr in the treatment group containing Bailing Capsule were lower than those in the control group. In terms of inflammatory indicators, hs-CRP, IL-6, and TNF-α, the treatment group containing Bailing Capsule also exhibited lower levels than the control group. Based on network pharmacology analysis, we identified 190 common targets of Bailing Capsule and CKD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that the pharmacological mechanism of Bailing Capsule might be related to immune response, inflammatory response, vascular endothelial damage, cell proliferation, and fibrosis. This demonstrates that Bailing Capsule can exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for its use.

Acute kidney injury (AKI) is associated with immune cell activation and inflammation. However, the putative pathogenic mechanisms of this injury have not been thoroughly investigated. Natural killer (NK) cells play an important role in immune regulation; however, whether NK cells regulate AKI remains unclear. Cordyceps sinensis (CS), a modern Chinese patented medicine preparation, has been widely used in treating patients with chronic kidney disease (CKD) owing to its anti-inflammatory effects and maintenance of immune homeostasis. Whether 2\'-deoxyadenosine, a major active component in CS, can ameliorate renal AKI by regulating immunity, particularly in NK cells, has not been reported. This study is the first to demonstrate how NK cells promote AKI by releasing perforin, interferon-gamma (IFN-γ) and other inflammatory factors in vivo and in vitro. Differential gene expression between AKI and normal tissues was assessed using bioinformatic analyses. Quantitative real-time PCR, western blotting, and immunohistochemical staining were used to detect target protein mRNA and protein expression. Levels of inflammatory factors were measured using enzyme-linked immunosorbent assay. We found the high doses of the 2\'-deoxyadenosine treatment significantly alleviated FA-induced renal damage in vivo, and alleviated the NK cells of renal injury by activating the STING/IRF3 pathway to inhibit perforin release in vitro. The results showed that 2\'-deoxyadenosine could mitigate AKI by downregulating the activity of NK cells (by decreasing the expressions of perforin and IFN-γ) and inhibiting the stimulator of interferon genes and phosphorylated IFN regulatory factor 3. This may provide valuable evidence supporting the clinical use of CS in treating patients with AKI.

BACKGROUND: Cordyceps sinensis (CS) is a fungus parasitic on lepidopteran larvae which is often used to treat lung diseases and regulate immune function.
OBJECTIVE: This review aimed to evaluate the efficacy of CS in the adjuvant treatment of lung cancer.
METHODS: As of June 2022, the electronic database search was conducted in PubMed, EMBASE, Cochrane Library, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database and China Science Journal Database (VIP database). Randomized clinical trials (RCTs) that evaluated the efficacy of CS as an adjuvant treatment for lung cancer were included. After the quality evaluation, meta-analysis was performed with Stata 16.0 software.
RESULTS: A total of 12 RCTs with 928 patients were identified for this meta-analysis, which showed that as an adjuvant treatment, CS has the following advantages in the treatment of lung cancer: (1) Improved tumor response rate (TRR) (RR: 1.17， 95%CI: 1.05-1.29，P = 0.00); (2) improved immune function, including increased CD4 (MD: 4.98, 95%CI: 1.49-8.47, P = 0.01), CD8 (MD: 1.60, 95%CI: 0.40-2.81, P = 0.01, I2 = 0.00%), NK (MD: 4.17, 95%CI: 2.26-6.08, P = 0.00), IgA (MD: 1.29, 95%CI: 0.35-2.24, P = 0.01), IgG (MD: 3.95, 95%CI: 0.98-6.92, P = 0.01) and IgM (MD: 6.44, 95%CI: 0.63-12.26, P = 0.03); (3) improved patients\' quality of life based on the mean ± SD of Karnofsky Performance Status (KPS) (MD: 8.20, 95%CI: 6.87-9.53, P = 0.00); (4) reduced the incidence of adverse drug reactions (ADRs), including the incidence of myelosuppression (RR: 0.38, 95%CI: 0.19-0.75, P = 0.01), leukopenia (RR: 0.76, 95%CI: 0.63-0.92, P = 0.00), and thrombocytopenia (RR: 0.52, 95%CI: 0.31-0.86, P = 0.01) (5) reduced the incidence of radiation pneumonitis (RR: 0.74, 95%CI: 0.62-0.88, P = 0.00). However, the number of improved patients based on KPS (RR: 1.47, 95%CI: 0.98-2.20, P = 0.06) were similar between two groups, liver and renal damage (RR: 0.32, 95%CI: 0.09-1.10, P = 0.07) and gastrointestinal adverse reactions (RR: 0.80, 95%CI: 0.47-1.37, P = 0.42) as well. Subgroup analysis showed that CS could increase the TRR in the treatment with 6 g/d and 21 days/3-4 cycles.
CONCLUSIONS: Compared with conventional treatment, adjuvant treatment with CS of lung cancer not only improve TRR, QOL and immune function, but also reduce the incidence of ADRs and radiation pneumonitis. The optimal usage may be 6 g/d and 21 days/3 to 4 cycles.
UNASSIGNED: CRD42022333681.

Fresh and dried Cordyceps sinensis are widely used by the public for medicinal and health purposes. However, the differences between them have not been examined. In this study, fresh wild and artificial C. sinensis (WFC and AFC) were dried to obtain dried wild and artificial C. sinensis (WDC and ADC). Non-targeted GC-MS was used to analyze the metabolic profile characteristics of the four groups of samples. The results showed that air drying significantly altered the composition and content of C. sinensis, mainly in the form of higher abundance of organic acids and derivatives and lower abundance of lipids and lipid-like molecules in fresh C. sinensis. Hierarchical cluster analysis (HCA) and quantitative analyses showed that air drying increased the abundance of Valine, Zinniol, Urocanate, Vulpinic acid, and Uridine 5\'-diphosphate, and decreased Xanthotoxol, Vitexin-4-o-glucoside, Val-trp, and Wogonin. These differentially accumulated metabolites (DAMs) were also shown to be potential biomarkers for C. sinensis. KEGG enrichment analysis identified lysine biosynthesis as the most significantly enriched pathway. Annotation of these DAMs to lysine biosynthesis revealed that citrate cycle and pyruvate metabolism entered lysine biosynthesis via 2-oxohlutarate and Homocitrate, respectively, resulting in significant enrichment of L-saccharopine and L-lysine content was significantly higher. Alanine, aspartate, and Glutamate metabolism synthesized more L-aspartate to promote L-lysine synthesis. Thus, high levels of L-lysine result in lysine degradation and pymolysine, which are the most active metabolic pathways during the drying of fresh C. sinensis and indirectly lead to differences in metabolic profiles.

Cordyceps sinensis is a kind of valuable Chinese herbal medicine, and its quality and price depend on the place of origin. Building a traceability system for Cordyceps sinensis products is an effective way to protect Cordyceps sinensis geographical indication products and consumers. In this study, concentrations of 45 trace elements and stable C, N, and Pb isotopes were used to distinguish Cordyceps sinensis samples from different habitats and different varieties (natural and artificial). The results showed that there were significant differences in the isotope compositions of N and Pb and trace elements contents in the Cordyceps sinensis samples from different sources. Stepwise discriminant analysis was used to select effective traceability indicators, and three discriminant models were successfully established. A combination of Co, Sr, Cu, Tl, and Zr indexes was selected to distinguish the naturally grown samples from the artificially cultivated ones, with an overall cross-validation correctness rate of 90.0 %; while a combination of As, Cu, Rb, Tl, W, and Zr indexes was adopted to distinguish the naturally grown samples from different regions, with a corresponding 100.0 % overall cross-validation correctness rate. To simultaneously distinguish samples between natural and artificial and between different regions, a combination of As, Cu, Rb, Tl, U, W, and δ15N indexes was employed, with an overall cross-validation correctness rate of 89.3 %.