ObjectiveThis study aims to explore the effect of Feiyanning granules on ferroptosis in lung cancer cells and its regulatory function within the nuclear transcription factor E₂-related factor 2 （Nrf2）/mouse solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe cell counting kit-8 （CCK-8） method was used to detect the effect of Feiyanning granule on the proliferation of A549 lung cancer cells. A549 lung cancer cells were categorized into a blank group， a ferroptosis inhibitor-1 （Fer-1） group （10 μmol·L^-1）， a Feiyanning granules （600 mg·L^-1） group， and a Feiyanning granules + Fer-1 group. After 48 hours of intervention， the activity and morphology of the cells were observed. The CCK-8 method was employed to measure cell viability. Biochemical assays were carried out to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ions （Fe²⁺） in A549 cells. Western blot was utilized to evaluate the expression levels of Kelch-like ECH-associated protein 1 （Keap1）， Nrf2， SLC7A11， and GPX4 proteins. A549 lung cancer cells were categorized into a blank group and a Feiyanning Granule group （600 mg·L^-1）， and mitochondrial morphology was examined via transmission electron microscopy （TEM）. ResultsAfter the intervention of Feiyaning granules， the proliferation of A549 cells was significantly inhibited in a concentration-dependent manner compared with that in the blank group （P<0.01）. Compared with the blank group， the Feiyanning granules group exerted an significantly inhibitory effect on the viability of lung cancer cells （P<0.01）. Compared with that in the Feiyanning granules group， the cell viability in the Feiyanning granules +Fer-1 group was obviously restored （P<0.05）. Compared with the blank group， the Feiyanning Granule group showed a significant increase in the levels of ROS， MDA， and Fe²⁺ （P<0.01）， a significant decrease in the GSH level （P<0.01）， and facilitated ferroptosis. Compared with the blank group， the Feiyanning granules group showed significantly decreased expression of Nrf2， SLC7A11， and GPX4 proteins and enhanced expression of Keap1 （P<0.01）. Compared with those in the Feiyanning Granule group， the protein levels of Nrf2， SLC7A11， and GPX4 increased significantly （P<0.01）， and the expression of Keap1 decreased significantly in the Feiyanning granules + Fer-1 group （P<0.01）. Compared with the blank group， the Feiyaning granules group exhibited reduced mitochondrial size and increased matrix electron density. ConclusionFeiyanning granules can induce ferroptosis in lung cancer cells， and its underlying mechanism might be associated with the inhibition of the Nrf2/SLC7A11/GPX4 signaling pathway.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

To gain an in-depth understanding of the clinical application of Rehmanniae Radix during the Qing Dynasty and to clarify its specifications and corresponding therapeutic effects， this study took Rehmanniae Radix in the prescriptions documented in Research on Medical Cases of the Qing Imperial Court as the research subject. According to historical medical literature， a comprehensive investigation was conducted on the specifications， therapeutic efficacy， frequency of use， dosage， and seasonal patterns of Rehmanniae Radix employed by imperial physicians. The findings revealed that Rehmanniae Radix in the medical cases of the Qing court was primarily classified into three categories： Xiaoshengdi， Zhongshengdi， and Dashengdi. Xiaoshengdi was also referred to as Xishengdi or Cishengdi， all denoting dried Rehmanniae Radix. The term Xishengdi was inconsistently defined in the literature. It should refer to the slender variant of dried Rehmanniae Radix and was utilized as a specific specification in the medical cases of the Qing court. In contrast， the wild fresh roots of Rehmanniae Radix， described as "as slender as fingers"， were commonly documented as fresh Rehmanniae Radix in these medical cases. There were variations in Rehmanniae Radix size and grading between historical and contemporary standards. Furthermore， therapeutic differences were observed among Rehmanniae Radix specifications in the medical cases of the Qing court. Xiaoshengdi and Zhongshengdi exhibited slightly stronger blood-cooling and heat-clearing effects while maintaining a non-cloying Yin-nourishing property. In contrast， Dashengdi demonstrated a greater emphasis on Yin supplementation with relatively milder heat-clearing activity. In the medical cases of the Qing court， the dosage of Rehmanniae Radix in different specifications was usually 11.2-18.7 g per dose， typically administered twice daily. Rehmanniae Radix in different specifications exhibits variations in efficacy， which can provide evidence-based insights for precise clinical application.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

To gain an in-depth understanding of the clinical application of Rehmanniae Radix during the Qing Dynasty and to clarify its specifications and corresponding therapeutic effects， this study took Rehmanniae Radix in the prescriptions documented in Research on Medical Cases of the Qing Imperial Court as the research subject. According to historical medical literature， a comprehensive investigation was conducted on the specifications， therapeutic efficacy， frequency of use， dosage， and seasonal patterns of Rehmanniae Radix employed by imperial physicians. The findings revealed that Rehmanniae Radix in the medical cases of the Qing court was primarily classified into three categories： Xiaoshengdi， Zhongshengdi， and Dashengdi. Xiaoshengdi was also referred to as Xishengdi or Cishengdi， all denoting dried Rehmanniae Radix. The term Xishengdi was inconsistently defined in the literature. It should refer to the slender variant of dried Rehmanniae Radix and was utilized as a specific specification in the medical cases of the Qing court. In contrast， the wild fresh roots of Rehmanniae Radix， described as "as slender as fingers"， were commonly documented as fresh Rehmanniae Radix in these medical cases. There were variations in Rehmanniae Radix size and grading between historical and contemporary standards. Furthermore， therapeutic differences were observed among Rehmanniae Radix specifications in the medical cases of the Qing court. Xiaoshengdi and Zhongshengdi exhibited slightly stronger blood-cooling and heat-clearing effects while maintaining a non-cloying Yin-nourishing property. In contrast， Dashengdi demonstrated a greater emphasis on Yin supplementation with relatively milder heat-clearing activity. In the medical cases of the Qing court， the dosage of Rehmanniae Radix in different specifications was usually 11.2-18.7 g per dose， typically administered twice daily. Rehmanniae Radix in different specifications exhibits variations in efficacy， which can provide evidence-based insights for precise clinical application.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted the quality differences between wild Polygalae Radix（WPR） and cultivated Polygalae Radix（CPR） from the aspects of character， microscope and chemical composition by modern scientific and technological means， providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city， Shaanxi province from 1 to 6 years were collected， and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques， including character traits（length， weight， diameter）， cross-sectional microscopic features（proportions of cork， phloem， xylem， etc）， cell wall component content（hemicellulose， cellulose， lignin）， extracts content（water-soluble extract and alcohol-soluble extract）， carbohydrate content（starch， water-soluble polysaccharides）， contents of total flavonoids， total saponins and specific marker compounds（3，6′-disinapoyl sucrose， polygalaxanthone Ⅲ， tenuifoliside A， tenuifoliside C， sibiricose A₅ and A₆） and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to conduct comparative analysis of secondary metabolites in WPR and CPR， and multivariate statistical analysis such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to screen the key differential components of them. ResultsIn terms of appearance， there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books， featuring a wrinkled surface and grayish-brown appearance. However， CPR had a finer texture and a yellowish white appearance， with weight， length， and diameter increasing with longer cultivation periods. In terms of microscopy， WPR exhibited a thick cork layer with fissures in the phloem， whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections， while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components， the contents of water-soluble extract， starch and total saponins in WPR were inversely proportional to the root diameter， while the contents of water-soluble extract， water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR， while the contents of other major components showed no significant change pattern. Among the six indicator components， the average content of sibiricose A₅ in WPR was significantly higher than that of CPR， followed by slightly higher content of tenuifoliside A. In CPR， the relative content of 3，6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years， while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them， the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins， and for CPR with different planting years， the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character， microscopic structure and chemical composition， and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However， the longer the cultivation years of PR， the closer it is to the "thick wrinkles on the epidermis" of WPR， which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.

ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

Through consulting herbal medicine， medical books， and local chronicles from past dynasties to modern times， this paper systematically researched Spatholobi Caulis from name， origin， producing areas， harvesting， processing， usage， quality evaluation， functions and indications， providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research， Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning， Yunnan， and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them， K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians， mainly treating rheumatic pain and injuries caused by falls or blows， and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction， which had the functions of promoting blood circulation and replenishing blood， activating meridians and collaterals， and mainly used for treating anemia， irregular menstruation， and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently， the main production area of S. suberectus is Guangxi， while the main production area of K. interior is Yunnan. In the Qing dynasty， the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments， which was usually composed of the juice of it， safflower， angelica， and glutinous rice. But in modern times， Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface， with a higher number indicating better quality. Additionally， the presence of resinous secretions is also considered desirable. Based on the research findings， it is suggested that when developing famous classical formulas containing Spatholobi Caulis， the choice of the primary source should be S. suberectus or K. heteroclita， taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia， adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names， and the functions adjust to promote Qi circulation and relieve pain， disperse blood stasis and unblock collaterals， treating injuries caused by falls and bruises.

Diabetes mellitus type 2 (T2DM) is one of the most common metabolic diseases in the world and has a significant impact on the health of patients. As a key factor in cellular mechanical transduction, Piezo1 protein plays a crucial role in regulating the basic life activities of the body. By participating in energy metabolism, it not only promotes the improvement of basic metabolic rate, but also helps to maintain the stability of the internal environment of the body. The activation of Piezo1 pathway has a significant effect on the release of insulin by islet beta cells, and also plays an important role in the production of adipose tissue after food intake. This study reviews the effects of exercise intervention on the expression and function of Piezo1 protein, as well as its role in metabolic regulation and insulin level regulation in T2DM patients. The study showed that a modest exercise intervention activated Piezo1 signaling pathway, which improved insulin sensitivity and improved sugar metabolism. In addition, the activation of Piezo1 pathway is closely related to the metabolic regulation of adipose tissue, helping to regulate the differentiation and maturation of adipose cells, thereby affecting the metabolic function of adipose tissue. Based on a comprehensive analysis of existing literature, Piezo1 pathway is found to play a complex role in the pathogenesis of T2DM. Exercise intervention, as a non-drug therapy, provides a new strategy for the treatment of T2DM by activating Piezo1 signaling pathway. However, the exact mechanism of action of Piezo1 pathway in T2DM still needs further investigation. Future studies should focus on the interaction between the Piezo1 pathway and T2DM, and how to regulate the Piezo1 pathway to optimize treatment for T2DM. The effects of exercise intervention on Piezo1 protein and its role in metabolic regulation and insulin level regulation of T2DM patients were comprehensively analyzed in this paper, aiming to provide a new perspective for further research and development of therapeutic strategies for metabolic diseases such as diabetes and obesity.