Enhanced UV-B Radiation in Potato Stems and Leaves Promotes the Accumulation of Anthocyanins in Tubers.

Enhanced ultraviolet-B (UV-B) radiation promotes anthocyanin biosynthesis in leaves, flowers and fruits of plants. However, the effects and underlying mechanisms of enhanced UV-B radiation on the accumulation of anthocyanins in the tubers of potatoes (Solanum tuberosum L.) remain unclear. Herein, reciprocal grafting experiments were first conducted using colored and uncolored potatoes, demonstrating that the anthocyanins in potato tubers were synthesized in situ, and not transported from the leaves to the tubers. Furthermore, the enhanced UV-B radiation (2.5 kJ·m-2·d-1) on potato stems and leaves significantly increased the contents of total anthocyanin and monomeric pelargonidin and peonidin in the red-fleshed potato '21-1' tubers, compared to the untreated control. A comparative transcriptomic analysis showed that there were 2139 differentially expressed genes (DEGs) under UV-B treatment in comparison to the control, including 1724 up-regulated and 415 down-regulated genes. The anthocyanin-related enzymatic genes in the tubers such as PAL, C4H, 4CL, CHS, CHI, F3H, F3'5'H, ANS, UFGTs, and GSTs were up-regulated under UV-B treatment, except for a down-regulated F3'H. A known anthocyanin-related transcription factor StbHLH1 also showed a significantly higher expression level under UV-B treatment. Moreover, six differentially expressed MYB transcription factors were remarkably correlated to almost all anthocyanin-related enzymatic genes. Additionally, a DEGs enrichment analysis suggested that jasmonic acid might be a potential UV-B signaling molecule involved in the UV-B-induced tuber biosynthesis of anthocyanin. These results indicated that enhanced UV-B radiation in potato stems and leaves induced anthocyanin accumulation in the tubers by regulating the enzymatic genes and transcription factors involved in anthocyanin biosynthesis. This study provides novel insights into the mechanisms of enhanced UV-B radiation that regulate the anthocyanin biosynthesis in potato tubers.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats. / ä¸åŒç¼ºæ°§å¹²é¢„å¯¹ä½ŽåŽ‹ä½Žæ°§æ¨¡åž‹é¼ è¡€æ°”åŠçº¢ç»†èƒžç›¸å ³æŒ‡æ ‡çš„å½±å“.

OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS: Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

[CiteSpace knowledge map of research status and trends of Croci Stigma].

This study retrieved Croci Stigma related literature from CNKI, Wanfang, VIP, and Web of Science database, and used bibliometrics and CiteSpace 6.1.R2 software to analyze the published Croci Stigma related articles in Chinese and English from 2000 to 2022. The authors, research institutions, and keywords were visualized and analyzed, and the current status and development trend of Croci Stigma research was summarized by combining the information extraction methods. A total of 1 846 Chinese articles and 2 703 English articles were screened out and included. The results showed a generally steady increase in the number of Croci Stigma related articles. The results of the visualization analysis showed that there were more collaborations between researcher teams and major research institutions in English articles than Chinese articles. The Chinese articles was mainly published by China Pharmaceutical University, and most of the inter-institutional collaborations occurred in neighboring regions. The English articles was mainly published by Iranian institutions, and most of the cooperation occurred within the country, with less transnational cooperation. Keywords analysis showed that the research on Croci Stigma was mainly focused on chemical compositions, pharmacological effects, mechanisms, quality control, etc. It was predicted that the future research hotspots of Croci Stigma would mainly focus on pharmacological mechanism and clinical efficacy. The current research related to Croci Stigma still needs to be developed, cooperation should be strengthened, and more in-depth research should be conducted.

Exercise performance reduction and preventive measures in highland sports. / 高原运动效能降低及防治措施.

The plateau is a special environment with low pressure, low oxygen, low temperature, and high ultraviolet radiation. The exercise performance of people on the plateau is generally reduced, which seriously affects the life and health of people living in the plateau and entering the plateau. In recent years, the prevention and treatment of injury caused by high altitude hypoxia has attracted wide attention. It has shown that the higher the altitude with the longer the duration of exercise, the faster the stationing, the greater the impact on people's sports performance. Rapid entry into the plateau and long-term stay in the plateau have an impact on people's explosive power, endurance and fine operation. Advances in medical technology enable various prevention methods to be used to acclimate to high altitude environments. However, in vitro intervention methods are costly, easy to rebound and possess limited effects. Therefore, drug prevention and treatment is obviously a more economical choice. Chemical drugs increase the efficiency of high altitude exercise by improving the ischemic and hypoxic symptoms of the heart and brain, increasing lung ventilation and arterial oxygenation capacity, and accelerating the elimination of adverse product accumulation after exercise. Single Chinese medicine, Chinese patent medicine, and compound preparations can improve exercise performance by promoting body metabolism, improving muscle endurance, enhancing immunity, and other mechanisms. Traditional Chinese medicine has unique advantage and application prospect in improving plateau sports performance damage.

Medication rule of traditional Chinese medicine in the treatment of plateau hypoxia based on data mining. / 基于数据挖掘中药治疗高原性缺氧的组方规律.

OBJECTIVES: The development of traditional Chinese medicine (TCM) in the plateau area is relatively backward. There is a lack of system to analyze the effects of the special environment of plateau low pressure and hypoxia on human meridians qi and blood, as well as the etiology and pathogenesis of plateau hypoxic diseases. To analyze the composition rules of anti-hypoxia TCM formulation with data mining methods. METHODS: The experimental literatures related to high altitude hypoxia were searched in China National Knowledge Infrastructure (CNKI), Wanfang Med Online, VIP, China Biology Medicine disc and other databases, a standardized prescription database was established after screening and standardization of prescription data in the literature. The composition rules of these prescription including drug frequency, drug attributes, drug efficacy, drug combination, and core prescription were analyzed and displayed with visual charts. RESULTS: A total of 135 TCM prescriptions were included, and 229 flavored drugs were included. Among these prescriptions, the TCM with high frequency of use were Astragalus, Danshen, Ginseng, and Angelica, etc. Four natures of the TCM were mostly warm and calm. Five flavours of the TCM were mostly sweet, bitter, and pungent. And channel tropism of the TCM mostly entered the heart, lung, and liver meridians. The frequency combination of TCM was Astragalus-Danshen and Astragalus-Angelica. The core medicines of these prescriptions were Astragalus, Danshen, Angelica, Rhodiola, Goji, and Ginseng. TCM could alleviate symptoms such as chest tightness, chest pain, coughing and wheezing, coughing, vomiting, fatigue, and loss of appetite caused by hypoxia at high altitude. CONCLUSIONS: Through data mining, it is concluded that the prevention or treatment of plateau hypoxic diseases mostly utilized products can nourish blood, replenish qi and dispel stasis, and help yang and dispel qi, most of them are compatible with qi tonic drugs and blood circulation and stasis dissolving drugs, and pay attention to the combination of virtual and real, yin and yang.

Comparison of the pharmacokinetics of Crocin-I in normoxic and hypoxic rats.

An ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) method for the simultaneous determination of Crocin-I and its primary metabolites Crocetin was established, and a comparison of metabolic characteristics in vivo is made to Crocin-I and Crocetin in normoxic and hypoxic rats after intragastric administration. The acute hypoxic rat model was established by simulating high altitude environment in a hypobaric hypoxia animal experimental chamber. After intragastric administration of 400 mg•kg-1 Crocin-I. UPLC-Q-TOF-MS method was used to detect the plasma concentrations of Crocin-I and Crocetin in plasma at different times. Compared with normoxic rats, the area under the curve (AUC), mean residence time (MRT), time to peak (Tmax), half-life (T1/2) and plasma concentration (Cmax) of plasma Crocin-I in hypoxic rats were significantly increased (P < 0.01). The apparent distribution (Vz/F) and clearance (CLz/F) of plasma Crocin-I in hypoxic rats were significantly decreased (P < 0.01). Under hypoxic conditions, the pharmacokinetic parameters of Crocin-I and its metabolite Crocetin change significantly. The results provide a theoretical basis for the feasibility of Crocin-I for anti-hypoxia treatment in terms of pharmacokinetics and provide an essential experimental basis for optimizing the drug dosing regimen.

[Comparison of distribution of verbascoside in normoxic and hypoxic rats].

This study established a high performance liquid chromatography(HPLC) method for the simultaneous determination of verbascoside(VB) and its main metabolite caffeic acid(CA) in rat tissue samples. A low-pressure low-oxygen animal experimental chamber was used to simulate the plateau environment for establishing the hypoxic rat model. After intragastric administration of 300 mg·kg~(-1) VB, the normoxic and hypoxic rats were sacrificed for the collection of heart, liver, spleen, lung, kidney, brain, muscle, large intestine, small intestine, and stomach tissue samples at the time points of 30, 60, and 90 min. VB and CA concentrations in each tissue sample were measured by HPLC, and the distribution of VB and CA in normoxic and hypoxic rats was compared. The results showed that after intragastric administration, VB can be rapidly absorbed and distributed into various tissues including brain in both normoxic and hypoxic rats, indicating that VB can pass through the blood-brain barrier. In the gastrointestinal tract, VB was mainly distributed in small intestine, which suggested that the main absorption site of VB was small intestine. A large amount of VB was detected in muscle and lung, and only a small amount in other tissues. CA was detected in other tissues except brain, heart, and muscle. Small intestine had the most abundant CA, followed by stomach, large intestine, and kidney, and only a small amount of CA was detected in the liver, spleen, and lung(<50 ng·mL~(-1)). The results indicated that VB may be mainly absorbed and metabolized in the gastrointestinal tract to produce CA and was possibly excreted through kidney. Compared with normoxic rats, hypoxic rats had reduced and slow distribution of VB and increased ratio of VB concentration in tissue to plasma, which implied that the relative proportion of VB from systemic circulation to tissues was increased in hypoxic rats. This study provides a basis for the application of VB in anti-hypoxia therapy and for the formulation of anti-hypoxia dosing regimens.

Polysaccharide extracted from Potentilla anserina L ameliorate acute hypobaric hypoxia-induced brain impairment in rats.

High altitude cerebral edema (HACE) is a high altitude malady caused by acute hypobaric hypoxia (AHH), in which pathogenesis is associated with oxidative stress and inflammatory cytokines. Potentilla anserina L is mainly distributed in Tibetan Plateau, and its polysaccharide possesses many physiological and pharmacological properties. In the present study, the protective effect and potential treatment mechanism of Potentilla anserina L polysaccharide (PAP) in HACE were explored. First, we measured the brain water content and observed the pathological changes in brain tissues, furthermore, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH) were evaluated by kits. Finally, the protein contents and mRNA expressions of pro-inflammatory (IL-1ß, IL-6, TNF-α, vascular endothelial cell growth factor [VEGF], NF-κB, and hypoxia inducible factor-1 α [HIF-1α]) were detected by ELISA kits, RT-PCR, and western blotting. The results demonstrated that PAP reduced the brain water content, alleviated brain tissue injury, reduce the levels of MDA and NO, and increased the activity of SOD and GSH level. In addition, PAP blocking the NF-κB and HIF-1α signaling pathway activation inhibited the generation of downstream pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and VEGF). Therefore, PAP has a potential to treat and prevent of HACE by suppression of oxidative stress and inflammatory response.

Effect and mechanism of verbascoside on hypoxic memory injury in plateau.

Verbascoside is a water-soluble natural phenylethanoid glycoside and distributes widely in plants. It has been proved with antioxidant, neuroprotective, anti-inflammatory, antibacterial, and immunomodulatory bioactivities. In this experiment, the effect and mechanism of verbascoside on hypoxic memory injury were studied in a low-pressure and low-oxygen chamber. Verbascoside (50, 150, and 300 mg/kg) was intragastrically administered once a day for 7 days. On the fourth day, rats were placed in the chamber to simulate a 7,500 m high-altitude environment The eight-arm maze was used to test the memory ability. The levels of MDA, GSH, and T-SOD in plasma, brain-NH, and hippocampus were detected. The mRNA expression of mTOR, P70S6K, and 4E-BP1 in the hippocampus tissue was determined by PCR. The protein expression of P-mTOR, P-P70S6K, P-4E-BP1, and Cleaved Caspase-3 in the hippocampus tissue was determined by western blot. The results indicated that administration with verbascoside could obviously reduce the working memory error, reference memory error, total errors, and total time; relieve the neuron damage in CA1 region of the hippocampus; and decrease the oxidative stress correlation enzyme activity in plasma, brain, and hippocampus. The amelioration of verbascoside on high altitude-induced memory impairment may be associated with the adjustment of oxidative stress and mTOR signaling pathway.

Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism in Chronically Stressed Rats Fed a High-Fat Diet.

Modern lifestyle factors (high-caloric food rich in fat) and daily chronic stress are important risk factors for metabolic disturbances. Increased hypothalamic-pituitary-adrenal (HPA) axis activity and the subsequent excess production of glucocorticoids (GCs) in response to chronic stress (CS) leads to increases in metabolic complications, such as type 2 diabetes and insulin resistance (IR). Melatonin (MLT), which protects several regulatory components of the HPA axis from GC-induced deterioration, might improve glucose homeostasis. Piromelatine is a melatonin receptor-1/melatonin receptor-2 (MT1/MT2) agonist with high affinity for MLT receptors and a longer duration of action than MLT. The objective of the present study was to explore the potential effects of piromelatine on glucose and lipid metabolism and insulin sensitivity in rats with IR induced by a high-fat diet combined with CS (CF). The results showed that piromelatine prevented the suppression of body weight gain and energy intake induced by CF and normalized CF-induced hyperglycemia and homeostasis model assessment-IR index, which suggests that piromelatine prevented whole-body IR. Piromelatine also prevented CF-induced dysregulation of genes involved in glucose and lipid metabolism, including proinflammatory cytokines, in adipose tissue. In addition, piromelatine also attenuated CF-induced excess free corticosterone release, increased glucocorticoid receptor expression, and decreased 11ß-hydroxysteroid dehydrogenase-1 expression, suggesting that piromelatine might ameliorate impaired glucose metabolism and prevent IR by normalizing HPA-axis functions. In conclusion, piromelatine might be a novel therapeutic agent for glucose intolerance and IR.

A label-free colorimetric biosensor for sensitive detection of vascular endothelial growth factor-165.

Sensitive detection of a low abundant protein is essential for biomedical research and clinical diagnostics. Herein, we develop a label-free colorimetric biosensor for the sensitive detection of recombinant human vascular endothelial growth factor-165 (VEGF165). This biosensor consists of an aptamer-based hairpin probe, an assistant DNA-trigger duplex and a linear template. In the presence of VEGF165, the specific binding of VEGF165 with the aptamer-based hairpin probe results in the opening of a hairpin probe and the opened hairpin probe subsequently hybridizes with the single-stranded region of the assistant DNA-trigger duplex to initiate the strand displacement amplification (SDA) to yield abundant triggers. The released triggers can further function as the primers to anneal with the hairpin probe and lead to the opening of the hairpin structure, which subsequently hybridizes with the assistant DNA-trigger duplex to initiate the next round of SDA reaction and generates more triggers. Large amounts of triggers could be generated by the synergistic operation of dual SDA reaction, and the obtained triggers can initiate a new round of SDA reaction to yield numerous G-quadruplex DNAzymes, which subsequently catalyze the conversion of ABTS2- to ABTS˙- by H2O2 to yield a color change with the assistance of a cofactor hemin. In contrast, in the absence of target VEGF165, the hairpin probe, the assistant DNA-trigger duplex and the linear template can stably coexist in solution, and thus no color change is observed because no trigger can initiate SDA to generate the G-quadruplex DNAzyme. This biosensor has a low detection limit of 1.70 pM and a dynamic range over 3 orders of magnitude from 24.00 pM to 11.25 nM. Moreover, the biosensor shows excellent specificity toward the target VEGF165 and the entire reaction can be carried out in an isothermal manner without the involvement of a high precision thermal cycler, making the current assay extremely cost effective.

[Effects and HPA Axis Related Mechanism of Kaixin-San and Danggui-Shaoyao-San on Glucose and Lipid Metabolism in Chronic Stress Rats with High-fat Diet].

OBJECTIVE: To study the effects and potential mechanism of Kaixin-San and Danggui-Shaoyao-San on glucose and lipid metabolism in chronic stress rats fed with high-fat diet. METHODS: 50 male Wistar rats were randomly divided into normal control group (distilled water), high-fat diet with chronic stress group (distilled water), melatonin group(20 mg/kg), Kaixin-San group (445 mg/kg) and Danggui-Shaoyao-San group (3360 mg/kg). All drugs were orally administered. In addition to the normal control group, each group of rats were fed with high-fat, diet. Simultaneously, stress were carried out after drugs administration 1 h daily. The duration was lasted for six weeks. The rat body weight daily was recorded, and the 24 h period urine was collected to detect the level of urine corticosterone (CORT) after three weeks. The level of plasma intraperitoneal glucose tolerance (IVGTT) was detected after six weeks. Finally, rats were executed, and serum fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), insulin (INS), adrenocorticotropic hormone releasing hormone (CRH), adrenocorticotropic hormone (ACTH), CORT and melatonin ( MLT) were determined. The weight of adrenal gland, liver glycogen and muscle glycogen levels were detected. The adrenal gland index, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity index( ISI) were calculated. RESULTS: Compared with normal group, model rats body weight, IVGTT (120 min), plasm CORT were decreased significantly. Serum TG, TC, LDL-C and urine CORT after three weeks were increased significantly. Kaixin-San and Danggui- Shaoyao-San could regulate the above indexes. CONCLUSION: Kaixin-San and Danggui-Shaoyao-San may regulate the activity of HPA axis, and improve glucose and lipid metabolism disorder in model rats by increasing melatonin secretion.

[Isolation and identification of nine iridoid glycosides from Lamiophlomis rotata by HPLC combining PDA and MS].

OBJECTIVE: To establish a rapid chromatographic method to separate the iridoid glycosides from Lamioplomis rotata, and to identify the target compounds with PDA and MS. METHODS: Methanol-water gradient elution was used to separate and analyze the target compounds. The fluid fractions were gathered according to the chromatogram and dried with the nitrogen airflow. The mass fractions of the target compounds were determined with RP-HPLC and the structures were identified with PDA and MS. RESULTS: The purity of some compounds exceeded 90% and these 9 compounds were identified as iridoid glycosides, which were Phlorigidoside C (1), Schismoside (2), Sesamoside (3), Shanzhiside methylester (4), 6-O-Acetyl shanzhiside methylester (5), Phloyoside II (6), Penstemoside (7), Loganin (8) and 8-O-Acetyl shanzhiside methylester (9). CONCLUSION: The method is simple and practicable with high efficiency. It can be used to qualitative and quantitative analysis of the 9 iridoid glycosides in Lamiphlomis rotata and its preparations.

Pollen transcriptomic analysis provided insights into understanding the molecular mechanisms underlying grafting-induced improvement in potato fertility.

Introduction: Heterologous grafting has been proven to be a valid approach to improving potato fertility, especially when grafting potatoes with other Solanaceae family plants. However, the mechanisms underlying grafting-induced improvement in potato fertility are still unknown. Methods: In this study, a poor-fertility potato cultivar "Qingshu No. 9" (Q9) was grafted with a tomato cultivar "Zhongyan988" (ZY988) to study the effects of heterologous grafting in the former. The tuber yield was controlled by different grafting and cultivation approaches, and the correlation between tuber yield and pollen vigor was studied. Comparative transcriptomic analysis of the potential mechanisms of pollen in potato scion fertility changes. Result: Grafting with the tomato rootstock effectively promoted the flower and fruit formation in the scion potato and improved its pollen viability by 15%-20%. In addition, a significant negative correlation was observed between the potato tuber yield and pollen viability, suggesting a potential impact on the metabolic regulatory network related to tuber formation. From the comparative transcriptomic analysis between the pollens from Q9 self-grafted plants and Q9-tomato grafting scion, 513 differentially expressed genes (DEGs) were identified. These DEGs were found to be related to gametophyte and pollen development, carbohydrate metabolism, and protein processing. Thus, these DEGs might be involved in improved fertility after reduced tuberization in plants subjected to heterologous grafting. Discussion: Potato/tomato heterologous grafting significantly improved the pollen viability of scion potatoes and was associated with the absence of potato tubers. Heterologous grafting promotes the transcription of genes related to protein processing, carbohydrate metabolism, and pollen development in pollen cells, resulting in the production of fertile pollen. Our results provided initial clues to understanding the improvement of potato fertility using the heterologous grafting method, which might be a useful tool in assisted potato breeding.

Potential therapeutic effects of traditional Chinese medicine in acute mountain sickness: pathogenesis, mechanisms and future directions.

Background and objectives: Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS. Methods: Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed. Results: We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism. Conclusion: The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

Current perspectives and trend of computer-aided drug design: a review and bibliometric analysis.

AIM: Computer-aided drug design (CADD) is a drug design technique for computing ligand-receptor interactions and is involved in various stages of drug development. To better grasp the frontiers and hotspots of CADD, we conducted a review analysis through bibliometrics. METHODS: A systematic review of studies published between 2000 and 20 July 2023 was conducted following the PRISMA guidelines. Literature on CADD was selected from the Web of Science Core Collection. General information, publications, output trends, countries/regions, institutions, journals, keywords, and influential authors were visually analyzed using software such as Excel, VOSviewer, RStudio, and CiteSpace. RESULTS: A total of 2031 publications were included. These publications primarily originated from 99 countries or regions led by the U.S. and China. Among the contributors, MacKerell AD had the highest number of articles and the greatest influence. The Journal of Medicinal Chemistry was the most cited journal, whereas the Journal of Chemical Information and Modeling had the highest number of publications. CONCLUSIONS: Influential authors in the field were identified. Current research shows active collaboration between countries, institutions, and companies. CADD technologies such as homology modeling, pharmacophore modeling, quantitative conformational relationships, molecular docking, molecular dynamics simulation, binding free energy prediction, and high-throughput virtual screening can effectively improve the efficiency of new drug discovery. Artificial intelligence-assisted drug design and screening based on CADD represent key topics that will influence future development. Furthermore, this paper will be helpful in better understanding the frontiers and hotspots of CADD.

Ferroptosis pathways: Unveiling the neuroprotective power of cistache deserticola phenylethanoid glycosides.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease. AIM OF THE STUDY: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS. MATERIALS AND METHODS: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia. RESULTS: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe2+ efflux and regulating mitochondrial Fe2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer). CONCLUSIONS: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.

Iodine-induced synthetic method and pharmacokinetic study of cis- and trans-crocetin.

Objective: This experiment aimed to obtain the relatively rare cis-crocetin isomer from natural plants, which predominantly exist in the more stable all-trans configuration. This was achieved through iodine-induced isomerization, followed by purification and structural identification. The study also aimed to compare the pharmacokinetic differences between cis- and trans-crocetin in vivo. Methods: Trans-crocetin of high purity was extracted by hydrolysis from gardenia yellow pigment. Cis-crocetin was then synthesized through an optimized electrophilic addition reaction induced by elemental iodine, and subsequently separated and purified via silica gel column chromatography. Structural identification of cis-crocetin was determined using IR, UV, and NMR techniques. In vivo pharmacokinetic studies were conducted for both cis- and trans-crocetin. In addition to this, we have conducted a comparative study on the in vivo anti-hypoxic activity of trans- and cis-crocetin. Results: Under the selected reaction conditions using DMF as the solvent, with a concentration of 2.5 mg/mL for both trans-crocetin and the iodine solution, and adjusting the illumination time according to the amount of trans-crocetin, the rate of iodine-induced isomerization was the fastest. Cis-crocetin was successfully obtained and, after purification, its structure was identified and found to be consistent with reported data. Cis-crocetin exhibited a faster absorption rate and higher bioavailability, and despite its shorter half-life, it could partially convert to trans-crocetin in the body, thereby extending the duration of the drug's action within the body to some extent. Conclusion: This study accomplished the successful preparation and structural identification of cis-crocetin. Additionally, through pharmacokinetic studies, it uncovered notable variations in bioavailability between cis- and trans-crocetin. These findings serve as a solid scientific foundation for future functional research and practical applications in this field.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.