Zhongguo Zhongyao Zazhi最新文献

This study was conducted in the context of national policy on high-quality promotion of global registration of traditional Chinese medicine(TCM) products, focusing on chemistry, manufacturing, and controls(CMC) requirement in registration application of botanical drug products in the USA. The information of the study was collected based on the current version of Botanical Drug Development Guidance for Industry and combined with case studies of two TCM products, namely Lianhua Qingwen Capsules and Compound Danshen Dripping Pills, registered in US Food and Drug Administration(USFDA) and four novel botanical drug products approved for marketing as prescription drugs. The present study analyzed CMC information based on the limited public information disclosed and highlighted the key points and difficulties of CMC study in the registration application of botanical drug products in USFDA, with the aim of providing reference for development of category 1.2 extracts and their formulations of TCM and natural products as well as registration application of TCM as botanical prescription drug products in USFDA.

This study constructed a core outcome set(COS) for traditional Chinese medicine(TCM) treatment of early-stage external cold and internal heat syndrome in respiratory viral infections, aiming to provide a reference for selecting outcomes in related clinical studies. A literature review was conducted to collect outcomes related to the early-stage external cold and internal heat syndrome in respiratory viral infections under TCM treatment from randomized controlled trials, systematic reviews, guidelines, and registered clinical trial protocols. Supplementary searches were performed in high-impact journals for systematic reviews on conventional medicine treatments for respiratory viral infections, as well as on the official websites of the Center for Drug Evaluation of the National Medical Products Administration and the US Food and Drug Administration, to develop the initial outcome pool. Two rounds of the Delphi surveys using a 9-point Likert scale were conducted to evaluate the importance of outcomes. The final outcomes were determined through a face-to-face expert consensus meeting. A total of 31 clinical studies, five systematic reviews, two guidelines, five registered clinical trial protocols, and eight new drug evaluation guidelines were included. After standardizing and sorting the outcomes, a pool of 34 outcomes was established. After two rounds of Delphi surveys, 17 outcomes were initially included. After the expert consensus meeting, 10 core outcome indicators were finally determined, including rate of progression to severe cases, time to major symptom improvement, time to resolution of all symptoms, dosage of antipyretic and analgesic medications, incidence of adverse events, time to viral clearance, mortality rate, quality of life, length of hospital stay, and time to normalization of body temperature.

Elucidating the effects of understory environmental factors on the yield and active constituent content of medicinal plants is essential for standardizing understory cultivation techniques in medicinal plant production. This study focused on Epimedium pubescens cultivated under forest canopies. By dynamically monitoring understory environmental factors across three plantations(Phellodendron amurense, Camptotheca acuminata, and Phoebe zhennan) and open-field cultivation(CK), this study assessed variations on different spatial scales(varying forest stands and understory positions) and temporal scales. Dynamic sampling and analysis of E. pubescens yields and flavonol glycoside content were conducted, elucidating the dynamic variation characteristics and influencing factors of both the yield and active constituent content of E. pubescens in understory cultivation. The results demonstrated that:(1)The spatial variations in understory environmental factors depended on tree species characteristics and stand density, while maintaining consistent patterns across temporal scales.(2)The yields of E. pubescens and the total flavonol glycoside content in the inter-row space of the three plantations were comparable to those of CK, while the yield of E. pubescens in the inter-row space increased by 90%(P. amurense), 101%(C. acuminata), and 107%(P. zhennan), respectively, compared with that under the canopy.(3)Understory air humidity was the environmental factor contributing most significantly to the yield formation of E. pubescens. The harvest yield could be quantitatively expressed by an exponential function of air humidity(y=0.167 7e~(0.072 4x), P<0.05, R~2=0.45). These findings provide theoretical guidance and technical support for the understory cultivation of E. pubescens and similar medicinal plants.

This study aims to investigate the role and mechanism of Shengmai Injection in oxygen-glucose deprivation/reoxygenation(OGD/R) microvascular endothelial cell injury based on mitochondrial dysfunction mediated by thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)/interleukin(IL)-1β signaling pathways. Human cardiac microvascular endothelial cells(CMEC) were cultured in vitro to establish the OGD/R model, and the experiments were performed in a normal group, a OGD/R group, OGD/R+low-dose(10 μL·mL~(-1)) and high-dose(30 μL·mL~(-1)) groups of Shengmai Injection, and OGD/R+mitochondria-targeted antioxidant agent(Mito-Tempo, 10 μmol·L~(-1)) group. The cell counting kit-8(CCK-8) method was used to screen the effective dose of Shengmai Injection on cells. The levels of IL-1β and nitric oxide(NO), along with the activity of endothelial nitric oxide synthase(eNOS) in cell supernatants, were measured by enzyme-linked immunosorbent assay(ELISA) across all groups. Additionally, the effects of low-and high-dose SMI on IL-1β, NO, and eNOS levels in cells were assessed in the absence of OGD/R treatment. In vitro blood vessel formation assay, cell scratch assay, and Transwell cell migration assay were performed to observe the effects of Shengmai Injection on cell tube formation and migration ability. The Annexin V-FITC apoptosis kit was used to detect the level of apoptosis. The fluorescent probe method and flow cytometry were used to detect the level of reactive oxygen species(ROS) of cells in each group, and the JC-1 mitochondrial membrane potential detection kit was used to detect the mitochondrial membrane potential levels in cells. The mRNA expression of related genes in the TXNIP/NLRP3/IL-1β signaling pathways was measured by using reverse transcription quantitative polymerase chain reaction(RT-qPCR). The expression of TXNIP, NLRP3, IL-1β, cleaved caspase-1, pro-caspase-3, and cleaved caspase-3 proteins was detected by Western blot, and the expression of NLRP3 and cleaved caspase-3 proteins was measured by immunofluorescence. The results showed that compared with the normal group, SMI-H(30 μL·mL~(-1)) significantly increased NO and eNOS levels without OGD/R treatment, but had minimal effect on IL-1β levels; compared with the OGD/R group, after model establishment, IL-1β level was significantly reduced, NO and eNOS levels were increased, cell tubularity, migration and cell viability were significantly increased, apoptosis rate and ROS level were significantly reduced, and mitochondrial membrane potential was increased in all groups, the expression levels of TXNIP,NLRP3,IL-1β,and cleaved caspase-1 genes and proteins were decreased, while the ratio of pro-caspase-3 to cleaved caspase-3 was increased. In conclusion, Shengmai Injection can ameliorate cell injury induced by OGD/R. Its mechanism of action may be associated with the inhibition of TXNIP/NLRP3/IL-1β signaling pathways and amelioration of mitochondrial dysfunction.

Ulcerative colitis(UC) is a chronic relapsing inflammatory disease of the intestines that primarily involves the colonic mucosa. More serious adverse reactions often accompany drugs used clinically for the treatment of UC. Glycyrrhizae Radix et Rhizoma, as a traditional Chinese medicine in China, has pharmacological effects such as anti-inflammatory, immune-regulating and antioxidant damage, which are very beneficial for the treatment of UC. In this study, we investigated the mechanism of action of Glycyrrhizae Radix et Rhizoma and its endophytes in treating UC by regulating the intestinal flora and the balance of T-cell 17(Th17)/regulatory T-cells(Treg) by establishing a UC rat model. Sixty-four specific pathogen free(SPF) SD rats were selected to establish UC rat model using trinitrobenzene sulfonic acid(TNBS) except for blank group, which was then randomly divided into model group, salicylazosulfapyridine group, licorice alcohol extract(LAE)-high,-medium, and-low dosage groups, lactobacillus rhamnosus group, and licorice endophyte(JTZB55) group, were given the appropriate drugs. The therapeutic effects of licorice and its endophytes were evaluated based on general condition, disease activity index(DAI) score, colon length, body weight, and hematoxylin-eosin(HE) stainning colon histopathological sections. Flow cytometry was used to detect Th17/Treg cell apoptosis. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect the expression levels of retinoic acid-related orphan receptor(ROR-γt) and forkhead frameshift protein(Foxp3). And changes in intestinal flora were detected using 16S rRNA technology. The results showed that Glycyrrhizae Radix et Rhizoma and its endophytes could effectively alleviate the deterioration of TNBS-induced colitis. Among them, LAE and JTZB55 could play an immunomodulatory role by regulating cytokines [interleukin(IL)-6, IL-17A, IL-10] to restore the balance of TNBS-induced imbalance of Th17/Treg cells.16S rRNA assay showed that the intestinal flora structure of the UC rats after the treatment with LAE and JTZB55 was significantly improved. In conclusion, LAE and JTZB55 can inhibit inflammation, regulate the balance of Th17/Treg cells and improve the intestinal flora in UC rats, which can effectively alleviate TNBS-induced UC.

Investigating optimal reference genes and expression patterns of key enzyme genes in terpenoid biosynthesis in Curcuma kwangsiensis across different developmental stages and tissues, this study selected 13 candidate reference genes(including ACTIN1, ACTIN2, ACTIN3, EF1, EF2, EF3, EF4, GAPDH1, GAPDH2, β-TUB, UBC, CYP1, and CYP2) and evaluated their stability by using ΔCT, GeNorm, NormFinder, BestKeeper, and RefFinder, with tuberous roots, rhizomes, leaves, and petioles at different developmental stages taken as experimental materials. The reliability of the reference genes was validated by detecting the expression of CkHMGR1. EF2 gene was identified as the most suitable reference gene in tissues of C. kwangsiensis across different developmental stages. Transcriptomic and metabolomic data were used to screen key enzyme genes involved in terpenoid biosynthesis, and their expression patterns in different tissues of C. kwangsiensis across different developmental stages were analyzed with EF2 gene as the reference gene. The results revealed that the expression patterns of 17 key enzyme genes(including CkHMGR1, CkHMGR2, CkDXS1, CkDXS2, CkDXR1, CkCMK1, CkHDS1, CkHDS2, CkHDS3, CkHDS4, CkHDR1, CkHDR2, CkHDR3, CkTPS1, CkTPS2, CkTPS3, and CkTPS4) exhibited significant differences across various tissues and developmental stages. Most genes showed high expression during the middle to late developmental stages of tuberous root and rhizome. Notably, CkTPS1 and CkTPS4 exhibited high expression during the late developmental stages of tuberous root and rhizome. This study lays a foundation for functional validation of key enzyme genes and elucidation of the terpenoid biosynthesis pathway in C. kwangsiensis.

Medicinal plants represent a critical component of natural resources and play a vital role in global healthcare and therapeutic systems. Saposhnikovia divaricata, a well-known traditional medicinal plant, exhibits ecological and quality suitability that is strongly influenced by various environmental factors. To investigate the suitable distribution and accumulation patterns of active components in S. divaricata in Mongolia, this study integrated climatic, soil, and topographic variables to evaluate its habitat suitability by using both the MaxEnt model and the Biomod2 ensemble modeling approach. The predictive performance of the two models was compared. High-performance liquid chromatography(HPLC) was employed to quantify the active components in collected S. divaricata samples, enabling a comprehensive quality assessment. The results demonstrated that the MaxEnt model achieved an area under curve(AUC) of 0.933 and a true skill statistic(TSS) value of 0.737, while the Biomod2 ensemble model showed improved performance with an AUC of 0.957 and a TSS value of 0.741. The most suitable regions for the growth of S. divaricata were identified as Dornod, Khentii, Selenge, Darkhan-Uul, Bulgan, Orkhon, and T9v provinces. Ecological suitability was primarily influenced by elevation(ELEVATION), precipitation during the warmest quarter(BIO18), and annual mean temperature(BIO1). The accumulation of prim-O-glucosylcimifugin was closely related to temperature, precipitation, and soil particle size, while the content of 5-O-methylvisammioside was largely influenced by precipitation and soil physicochemical properties, including base saturation, aluminum saturation, and cation exchange capacity. This study provides guidance for seed introduction, cultivation, and standardized production of S. divaricata in Mongolia.

The traditional Chinese medicine(TCM) known as Beimu, including Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, Fritillariae Hupehensis Bulbus, Fritillariae Ussuriensis Bulbus, and Fritillariae Pallidiflorae Bulbus, possesses significant medicinal value with a long history of use, has a substantial market demand, and serves as a crucial subject of research. According to Chinese Pharmacopoeia(2020 edition), the dried bulbs of eleven Fritillaria species are the sources of Beimu. The characteristic and active ingredients steroidal alkaloids in Fritillaria species are among the natural products to be investigated earliest globally. These compounds play a pivotal role in the development of natural products and demonstrate a diverse range of pharmacological effects. This review delves into the natural products found in Fritillaria species and their pharmacological properties. Based on literature and the research achievements of the authors' research group, this paper comprehensively summarizes, for the first time, the structural types, physicochemical properties, and spectral characteristics of steroidal alkaloids in Fritillaria species. In-depth analyses reveal that Fritillaria species contain a rich diversity of steroidal alkaloids with varied structural types, and these active ingredients hold promising potential for research on antitussive, anti-pneumonia, and acute lung injury treatment. Additionally, developing effective quality control methods based on steroidal alkaloids is crucial for the development of TCM Beimu and the standardized management of its related cultivated species.