[Pseudo-targeted metabolomics study of immune stress-mediated idiosyncratic liver injury induced by synergistic effects of bavachin and epimedin B].

Chinese patent medicine preparations containing Epimedii Folium and Psoraleae Fructus have been associated with the occurrence of idiosyncratic drug-induced liver injury(IDILI). However, the specific toxic biomarkers and mechanisms underlying these effects remain unclear. This study aimed to comprehensively assess the impact of bavachin and epimedin B, two principal consti-tuents found in Psoraleae Fructus and Epimedii Folium, on an IDILI model induced by tumor necrosis factor-α(TNF-α) treatment, both in vitro and in vivo. To evaluate the extent of liver injury, various parameters were assessed. Lactate dehydrogenase(LDH) release in the cell culture supernatant, as well as the levels of alanine aminotransferase(ALT) and aspartate transaminase(AST) in mouse plasma were measured. Additionally, histological analysis employing hematoxylin-eosin staining was performed to observe liver tissue changes indicative of the severity of liver injury. Furthermore, a pseudo-targeted metabolomics approach was employed, followed by multivariate analysis, to identify differential metabolites. These identified metabolites were subsequently subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The results showed that at the cellular level, after 2 hours of TNF-α stimulation, bavachin significantly increased the release of LDH in HepG2 cells compared to the normal group and the group treated alone; after the combination of bavachin and epimedin B, the release of LDH further significantly increased on the original basis. Similarly, although the individual or combination treatments of bavachin and epimedin B did not induce liver injury in normal mice, the combination of both drugs induced marked liver injury in TNF-α treated mice, leading to a significant elevation in plasma AST and ALT levels and substantial infiltration of inflammatory immune cells in the liver tissue. Pseudo-targeted metabolomics analysis identified seven common differential metabolites. Among these, D-glucosamine-6-phosphate, N1-methyl-2-pyridone-5-carboxamide, 17beta-nitro-5a-androstane, irisolidone-7-O-glucuronide, and N-(1-deoxy-1-fructosyl) valine emerged as potential biomarkers, with an area under the curve(AUC) exceeding 0.9. Furthermore, our results suggest that the metabolism of nicotinic acid and nicotinamide, as well as the linoleic acid metabolic pathway, may play pivotal roles in bavachin and epimedin B-induced IDILI. In conclusion, within an immune-stressed environment mediated by TNF-α, bavachin and epimedin B appear to induce IDILI through disruptions in metabolic processes.

Increased panicle nitrogen application improves rice yield by alleviating high-temperature damage during panicle initiation to anther development.

The grain yield is closely associated with spikelet fertility in rice (Oryza sativa L.) under high temperatures, and nitrogen (N) plays a crucial role in yield formation. To investigate the effect of panicle N application on yield formation under high temperatures at the panicle initiation stage, two rice varieties [Liangyoupeijiu (LYPJ, heat susceptible) and Shanyou63 (SY63, heat tolerant)] were grown and exposed to high daytime temperature (HT) and control temperature (Control) during the panicle initiation stage. Low (LPN) and high (HPN) panicle N applications were conducted. HT markedly decreased the yields by 87% at LPN and 48% at HPN in LYPJ and 31% at LPN and 36% at HPN in SY63. The decrease in grain yield under HT was primarily attributed to the decline in spikelet fertility, HPN increased spikelet fertility. HT resulted in the abnormal development of anthers, which included disordered, enlarged, and broken anther wall layers, degraded and irregularly shaped microspores, delayed tapetum degradation, less vacuolated microspores per locule, abnormal and aborted pollen grains; however, HPN improved the development of anthers under HT, particularly in LYPJ. A high rate of evapotranspiration resulted in an approximately 1°C decrease in panicle temperatures at HPN compared with that at LPN in both varieties under HT. Overall, these results demonstrate that the increased panicle N application favors normal anther development in LYPJ by decreasing the panicle temperature, which results in high pollen viability and spikelet fertility, and consequently less yield loss under HT.

Rapid classification and identification of chemical compositions of Pu-zhi-hui-ling decoction by UHPLC-Q-Orbitrap HRMS.

Pu-zhi-hui-ling decoction (PZHLD) is a traditional Chinese medicine (TCM) formula for the treatment of Alzheimer's disease (AD), but its chemical composition has not been reported. In this study, we aimed to establish a mass spectrometry (MS) analysis method for rapid classification and identification of the chemical constituents in PZHLD. The sample was analysed by ultrahigh-performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The chemical constituents of PZHLD were identified based on accurate MS data, fragmentation characteristics of MS/MS, and reference information described in the literature. A total of 123 chemical constituents were identified. In addition, we summarised the fragmentation pathways of the chemical constituents in PZHLD. Our finding might lay the foundation for the further pharmacodynamic study and clinical application of PZHLD.

Panax japonicus C.A. Meyer: a comprehensive review on botany, phytochemistry, pharmacology, pharmacokinetics and authentication.

BACKGROUND: Panax japonicus C.A. Meyer (Zhujieshen) is widely used in traditional medicine as a tonic hemostatic and anti-inflammatory agent in China, Japan, and Korea. Furthermore, it is used as an important substitute for ginseng roots by minority ethnic groups in China. The purpose of this review is to summarize the latest research on Zhujieshen in recent years, aiming at providing a systematic overview of the current knowledge, and perspectives for future research and exploitation. MAIN BODY: This review examines the research advances in botanical profile, phytochemicals, pharmacology, pharmacokinetics, and authentication of Zhujieshen. Various compounds have been reported as active components, mainly including saponins, volatile oils, and polysaccharides. Pharmacological investigations have demonstrated that Zhujieshen is an important herb with significant bioactivities, such as anti-inflammatory, hepato-protective, cardio-protective, neuro-protective, anti-tumor, anti-oxidant, anti-thrombotic and immunomodulatory activities. CONCLUSION: Currently, research on Zhujieshen is in the preliminary stages, and further research is required to understand the active compounds present and mechanisms of action. We hope that this comprehensive review of Zhujieshen will serve as a background for future research and exploitation.

Sijunzi Tang improves gefitinib resistance by regulating glutamine metabolism.

Lung cancer is a major health concern and significant barrier to human well-being and social development. Although targeted therapy has shown remarkable progress in the treatment of lung cancer, the emergence of drug resistance has limited its clinical efficacy. Sijunzi Tang (SJZ) is a classical Chinese herbal formula known for tonifying qi and nourishing the lungs, has been recognized for its potential in lung cancer management. However, the underlying mechanism of its combined use with anti-cancer drugs remains unclear. Here, we investigated the anti-lung cancer efficacy and underlying mechanisms of the combination of gefitinib and SJZ in gefitinib-resistant human lung adenocarcinoma cells (PC-9/GR). We conducted in vitro and in vivo experiments using histopathology and targeted metabolomics approaches. Our results demonstrated that the combination of SJZ and gefitinib exhibited synergistic effects on tumor growth inhibition in PC-9/GR-bearing nude mice. Notably, the co-administration of SJZ and gefitinib synergistically promoted tumor cell apoptosis, potentially through the regulation of BAX and BCL-2 expression. Immunohistochemistry and western blot analysis found down-regulation of GLS, GS, and SLC1A5 expression in the co-administration group compared to the control and the individual treatment groups. Targeted metabolomics revealed significant alterations in the plasma glutamine metabolic markers glutamine, alanine, succinate, glutamate, and pyruvate. Of the glutamine metabolism markers measured in tumor tissues, glutamine and pyruvate demonstrated significant differences across the treatment groups. These findings suggest that administration of SJZ improves gefitinib resistance in the treatment of lung cancer without toxic effects. Moreover, SJZ may affect glutamine metabolism by regulating key targets involved in glutamine metabolism (SLC1A5, GLS, and GS) and modulating the levels of related metabolic markers, ultimately reducing gefitinib resistance.

Near-Infrared Self-Assembled Hydroxyl Radical Generator Based on Photoinduced Cascade Electron Transfer for Hypoxic Tumor Phototherapy.

The hydroxyl radical (•OH) is an extremely potent reactive oxygen species that plays a crucial role in photooxidations within the realm of hypoxic tumor therapy. However, the current methods for •OH photogeneration typically rely on inorganic materials that require UV/vis light excitation. Consequently, photogenerators based on organic molecules, especially those utilizing near-infrared (NIR) light excitation, are rare. In this study, the concept of photoinduced cascade charge transfer (PICET), which utilizes NIR heavy-atom-free photosensitizers (ANOR-Cy5) to generate •OH is introduced. The ANOR-Cy5 photosensitizer, with its flexible hydrophobic structure, enables the formation of nanoparticles in aqueous solutions through molecular assembly. PICET involves a symmetry-breaking charge separation-induced localized charge-separated state, transitioning to a delocalized charge-separated state, which governs the efficiency of •OH generation. Thanks to the oxygen-independent nature of •OH generation and its robust oxidative properties, the ANOR-Cy5-based photosensitizer demonstrates highly effective photoinduced anti-cancer effects, even under severely hypoxic conditions. This discovery emphasizes the potential for achieving •OH photogeneration using a single organic molecule through the engineering of molecular self-assembly, thereby opening up new possibilities for phototherapy and beyond.

Methylprednisolone sodium succinate retroauricular injection combined with acupuncture in the treatment of Bell's Palsy.

Background: Retroauricular injection is a local steroid hormone administration method commonly used to treat deafness or tinnitus. The acute stage of Bell's Palsy is an acute disease that requires steroid therapy. Retroauricular injection may replace oral administration of steroid hormones in the treatment of this disease as well as reduce the occurrence of adverse reactions. Methods: This study included patients with Bell's Palsy within seven days of onset. A total of 120 patients were enrolled as the study subjects and randomly divided into two groups: the experimental group and the control group. Both groups received routine acupuncture treatment and took a traditional Chinese medicine decoction corresponding with the syndrome type. Methylprednisolone sodium succinate was injected into the bone surface of retroauricula in the experimental group, and prednisone acetate was orally administered in the control group. The main outcome indicators were the House-Brackmann (HB) grade, the facial disability index (FDI), and time of postauricular pain after one month of treatment. Results: There were no significant differences in the HB grade (2.00 ± 1.06 vs. 1.88 ± 1.06, P=), FDIP (97.25 ± 6.00 vs. 97.17 ± 7.39, P=), and FDIS (0.60 ± 3.02 vs. 1.33 ± 4.27, P=) at 30 days after treatment between the two groups (P > 0.05). Postauricular pain disappeared earlier in the experimental group (3.66 ± 1.67 days) than in the control group (6.31 ± 2.34); the difference was statistically significant (P ≤ 0.001). The adverse reaction rate was lower in the experimental group (15.00%) than in the control group (21.66%). Interpretation: Although the dose of steroid hormone injected into the bone surface of retroauricula in the treatment of Bell's Palsy is lower than the administered dose of oral hormones, it has the same curative effect; however, it has a better effect regarding to the duration of postauricular pain and adverse reactions.

Safety monitoring of oral iron supplements in pregnant women with anemia: a multi-center observational clinical study.

Aims: To investigate the safety of oral iron therapy in pregnant women with iron-deficiency anemia (IDA) in the real world. Methods: A retrospective analysis was performed on 1792 pregnant patients with IDA who received oral iron supplements from 12 hospitals in Shandong Province from 1 April to 31 June 2021; follow-up and adverse reactions were recorded. They were divided into six groups according to the treatment drugs. Results: The overall adverse reaction rate was 15.4%, and the main adverse reaction site was the digestive system. The incidence of all kinds of oral iron adverse reactions from high to low in order: compound ferrous sulfate and folic acid tablets (21.88%); iron proteinsuccinylate oral solution (20.90%); ferrous succinate tablets (19.76%); ferrous succinate sustained-release tablets (18.00%); iron polysaccharide complex capsule (12.06%); and iron dextran oral solution (6.94%). It was found that there was a significant difference in the incidence of adverse reactions among the six drugs (p < 0.05). Pairwise comparison showed that the incidence of adverse reactions was higher in the iron proteinsuccinylate oral solution than that in the iron polysaccharide complex capsule (p < 0.05). There was no significant difference in the incidence of adverse reactions in different ages (p > 0.05), but there was a significant difference in the incidence of adverse reactions in different gestational ages (p < 0.05). In Adverse Drug Reaction (ADR) patients, the adverse reaction result of most patients is recovery or improvement, and there was no serious adverse reaction outcome such as sequela and death. Conclusion: All the adverse reactions of oral iron were mainly gastrointestinal adverse reactions, and no heavy adverse reactions were found. Iron proteinsuccinylate oral solution has a higher incidence of adverse reactions than iron polysaccharide complex capsule. The results showed that oral iron was safer for anemia patients during pregnancy.

Safety of oral iron in the treatment of iron-deficiency anemia during pregnancy Introduction: The safety of different oral iron agents varies. At present, the safety evaluation of iron supplements in the treatment of anemia during pregnancy is mainly focused on intravenous iron supplements, and there is no comprehensive study on the safety of commonly used oral iron supplements. This study compared the safety of six commonly used oral iron supplements in the treatment of iron-deficiency anemia during pregnancy, aiming to provide a reference for clinical medication. Methods: We conducted a study involving 1792 patients in 12 hospitals in Shandong Province from 1 April to 31 June 2021. Results: Among the six groups, 276 ADR patients reported 302 adverse reactions. There were significant differences in the rates of adverse reactions among the six oral iron agents, and the incidence of adverse reactions in the iron proteinsuccinylate oral solution was significantly higher than that of iron polysaccharide complex capsules. The main incidence of adverse reactions was constipation (6.96%), and most of the outcomes were cured or improved. Conclusion: In this study, there were no heavy adverse reactions. The incidence of adverse reactions of iron proteinsuccinylate oral was higher than that of iron polysaccharide compound capsule. The results showed that oral iron had a good safety in patients with anemia during pregnancy.

Improving Chuanxiong Rhizoma quality standards using an effect-constituent index based bioassay.

Chuanxiong Rhizoma is a traditional Chinese medicine (TCM) that is used to promote blood circulation. We set out to improve Chuanxiong Rhizoma quality standards using a bioassay-based Effect-constituent Index (ECI). We performed high performance liquid chromatography (HPLC) analysis to determine the chemical constituents of 10 Chuanxiong Rhizoma samples from different locations. We then constructed a direct bioassay method to investigate each sample's antiplatelet aggregation effects. To screen for active ingredients that promote antiplatelet aggregation, we carried out Pearson correlation analyses between biopotency and compounds identified in the HPLC data. We developed an ECI of platelet aggregation inhibition using a multi-indicator synthetic evaluation method based on the integration of biopotency and active constituents. To further assess the biopotency-based Chuanxiong Rhizoma quality evaluation result accuracy, we compared the ECI with the chemical indicator' method. Eight common chemical fingerprints peaks indicated notable content variation among samples. Biological evaluation showed that all 10 samples could inhibit platelet aggregation, although they had significantly different biological potencies. Using spectrum-effect relationships, we determined that Ligustilide was the significant active constituent responsible for antiplatelet aggregation. Using correlation analysis, we found that ECI correlated with the Chuanxiong Rhizoma extract's platelet aggregation inhibitory effect. Additionally, ECI proved to be a good indicator of Chuanxiong Rhizoma quality, whereas chemical indicators failed to distinguish and predict the biopotency-based quality grade. This work indicates that ECI is a useful tool for associating sample quality with chemical markers linked to TCM clinical effects. ECI also provides a paradigm for improving the quality control of other TCMs that invigorate blood circulation.

Metabolomics Combined with Network Pharmacology-Based Strategy to Reveal the Underlying Mechanism of Zhenhuang Submicron Emulsion in Treating Oropharyngeal Mucositis Complications of Radiation Therapy for Head and Neck Cancer.

Introduction: Head and neck tumors account for more than 6% of all cancers. The primary treatment for tumors of the head and neck is radiation therapy, which can induce oropharyngeal mucositis as a side effect. At present, there is no widely available therapeutic for the treatment of oropharyngeal mucositis in clinical practice. Based on the traditional prescription Liushen Wan, the pathogenesis and pathology, we developed a new Chinese medicine prescription and made Zhenhuang submicron emulsion (ZHSE) spray, which has an efficacious therapeutic effect for oropharyngeal mucositis. However, its mechanism is unclear. Methods: This research explored the mechanism behind the modulatory effects of ZHSE by a strategy of metabolomics and network pharmacology. Multivariate data analyses, including unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA), were performed. Potential biomarkers were identified depending on the mass-charge ratio of the selected compound. Statistical and pathway enrichment analysis was performed in the KEGG pathway database. Network pharmacology combining metabolomic analyses was conducted to illustrate the key targets and pathways. Results: Critical metabolic pathways were investigated, 56f biomarkers were enriched and key metabolites such as linoleic acid, 9,10-epoxyoctadecenoic acid, acetoacetic acid and citric acid were identified. A complex network of "compound-target-potential metabolite" interactions was drawn to illuminate the regulation of chemical constituents on key metabolites. These findings manifest that ZHSE regulates endogenous metabolite disorders during the treatment of oropharyngeal mucositis by various constituents, interacting with multiple targets associated with inflammation and pain. Conclusion: In this work, we determined several critical biomarkers and metabolic pathways and identified the possible regulatory mechanism by which ZHSE functions in the treatment of oropharyngeal mucositis. This study provides a new perspective on integrating metabolomics and network pharmacology for exploring improved therapy for head and neck tumors based on the traditional classic prescription of LSW.

Haplotype-resolved genome assembly of Bletilla striata (Thunb.) Reichb.f. to elucidate medicinal value.

Bletilla striata, commonly known as baiji, is a species used in traditional Chinese medicine; it is highly regarded for its medicinal applications and therefore has high economic value. Here, we report a high-quality haplotype-resolved genome of B. striata, haplotype A (2.37 Gb, with a scaffold N50 of 146.39 Mb and a contig N50 of 1.65 Mb) and haplotype B (2.43 Gb, with a scaffold N50 of 150.22 Mb and a contig N50 of 1.66 Mb), assembled from high-fidelity (HiFi) reads and chromosome conformation capture (Hi-C) reads. We find evidence that B. striata has undergone two whole-genome duplication (WGD) events: an ancient WGD event shared by most monocots and a recent WGD event unique to all orchids. We also reconstructed the ancestral orchid karyotype (AOK) of 18 ancient chromosomes and the evolutionary trajectories of 16 modern B. striata chromosomes. Comparative genomic analysis suggests that the expanded gene families of B. striata might play important roles in secondary metabolite biosynthesis and environmental adaptation. By combining genomic and transcriptomic data, we identified the 10 core members from nine gene families that were probably involved in B. striata polysaccharide (BSP) biosynthesis. Based on virus-induced gene silencing (VIGS) and yeast two-hybrid experiments, we present an MYB transcription factor (TF), BsMYB2, that can regulate BSP biosynthesis by directly interacting with eight key BSP-related genes: sacA1, HK1, scrK1, scrK2, GPI1, manA1, GMPP1 and UGP2_1. Our study will enhance the understanding of orchid evolution and accelerate the molecular-assisted breeding of B. striata for improving traits of medicinal value.

Xihuang Pill enhances anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway.

Lung cancer poses a serious threat to human health. Although targeted therapies have led to breakthroughs in the treatment of lung cancer, drug resistance and side effects limit their clinical applications. Xihuang pill (XHW), a classical anti-cancer traditional Chinese medicine formula, has been clinically proven to be an effective complementary therapy in the treatment of various of cancers. However, the underlying mechanism for its use in combination with anti-cancer drugs remains unclear. Here, we explored the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung cancer (LLC). We used gut microbiota and transcriptomics to elucidate the regulatory properties of XHW in improving anti-lung cancer effect of anlotinib. The results showed that combination treatment of XHW with Anlotinib significantly inhibited tumor growth in LLC-bearing mice. We found that XHW played a key role in the regulation of gut microbiota using 16 s rRNA sequencing analysis. Specifically, XHW increased the proportion of the beneficial bacteria Bacteroides and g_norank_f_Muribaculaceae. Based on transcriptomic analysis of tumor tissues, differentially expressed genes in the combination therapy group were related to biological processes concerning angiogenesis, such as regulation of blood vessel diameter, regulation of tube diameter, and regulation of tube size. Our data suggest that XWH enhances the anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Combination therapy with anlotinib and XHW may be a novel therapeutic strategy for lung cancer patients.

A Rationally Designed Building Block of the Putative Magnetoreceptor MagR.

The ability of animals to perceive guidance cues from Earth's magnetic field for orientation and navigation has been supported by a wealth of behavioral experiments, yet the nature of this sensory modality remains fascinatingly unresolved and wide open for discovery. MagR has been proposed as a putative magnetoreceptor based on its intrinsic magnetism and its complexation with a previously suggested key protein in magnetosensing, cryptochrome, to form a rod-like polymer structure. Here, we report a rationally designed single-chain tetramer of MagR (SctMagR), serving as the building block of the hierarchical assembly of MagR polymer. The magnetic trapping experiment and direct magnetic measurement of SctMagR demonstrated the possibility of magnetization of nonmagnetic cells via overexpressing a single protein, which has great potential in various applications. SctMagR, as reported in this study, serves as a prototype of designed magnetic biomaterials inspired by animal magnetoreception. The features of SctMagR provide insights into the unresolved origin of the intrinsic magnetic moment, which is of considerable interest in both biology and physics. © 2022 Bioelectromagnetics Society.

An Integrative Metabolomic and Network Pharmacology Study Revealing the Regulating Properties of Xihuang Pill That Improves Anlotinib Effects in Lung Cancer.

Lung cancer ranks as a leading cause of death. Although targeted therapies usually trigger profound initial patient responses, these effects are transient due to drug resistance and severe side effects. Xihuang Pill (XHW) is a popular Chinese medicine formula that might benefit cancer patients when used as a complementary therapy. However, its underlying mechanism when combined with anticancer drugs is not clearly understood. Here, we used an integrated strategy to reveal the regulatory properties of XHW in increasing the antitumor activity of anlotinib in lung cancer. We evaluated the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung carcinoma (LLC). We applied untargeted metabolomics to identify the differences metabolism and found that XHW improved the effects of anlotinib on lung cancer. The components and targets related to the effects of XHW treatment on lung cancer were obtained through network pharmacology. Then, by integrating the biologically active components of XHW and anlotinib as well as the treatment-responsive metabolites and their related targets, an interaction network was constructed to evaluate the combination therapy. Finally, important protein candidates for this response were verified by immunohistochemistry of tumor tissues. The results showed that XHW significantly improved the inhibitory effect of anlotinib on tumor growth in LLC-bearing mice. Additionally, 12 differentially-abundant metabolites were identified by untargeted metabolomics in the XHW/anlotinib group compared with the XHW or anlotinib groups, and they were mainly enriched in fatty acid metabolism, lipid metabolism and amino acid metabolism pathways. Anlotinib, 23 components in Shexiang, 2 components in Niuhuang, 30 components in Ruxiang and 60 components in Moyao work together to act on 30 targets to regulate hexadecanoic acid (also named palmitic acid), linoleic acid, lactosylceramide, adrenaline, arachidonic acid and lysoPC(18:1(9Z)). The results of immunohistochemistry showed that XHW combined with anlotinib reduced the expression of PDGFRA in tumors. Overall, the key metabolites of XHW that enhances the efficacy of anlotinib were regulated by a multicomponent and multitarget interaction network. Our results suggested that anlotinib combined with XHW may be a promising strategy for the treatment of lung cancer.

Effect of Single-Dose and Short-Term Administration of Si Jun Zi Tang on the Pharmacokinetics of Gefitinib in Rats.

BACKGROUND: Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula that has been described for approximately one thousand years, is often prescribed for cancer patients as a complementary therapy in China. However, the mechanism by which Si Jun Zi Tang enhances the efficacy of gefitinib is unclear. METHODS: We investigated how Si Jun Zi Tang affected the pharmacokinetics of gefitinib in rats. A rapid, specific, and reliable ultra-performance liquid chromatography method with mass spectrometry was established to determine the plasma concentration of gefitinib. RESULTS: The results showed that a single intragastrically administered dose of Si Jun Zi Tang increased the pharmacokinetic parameters of gefitinib (C max, 3156.13 µg/L; A UC, 46281.5 µg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (C max, 1352.07 µg/L; AUC, 11823.7 µg/L/h). Si Jun Zi Tang could also alter the pharmacokinetics of gefitinib by prolonging the time to reach C max. CONCLUSIONS: Potential pharmacokinetic interactions between gefitinib and SJZ were evaluated, and SJZ extended T max and T1/2 and increased the C max and AUC of gefitinib. Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib.

Thesium chinense Turcz.: An ethnomedical, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Thesium chinense Turcz. has been used to treat mastitis, pulmonitis, tonsillitis, iaryngopharyngitis and upper respiratory tract infections in the indigenous medicine of China for a long history. Presently, several pharmaceutics prepared by this medical herb have been clinically used for the therapy of infectious diseases. AIM OF THE REVIEW: This review aims to comprehensively summarize the current researches on the ethnomedical, phytochemical and pharmacological aspects of T. chinense, and discuss their possible opportunities for the future research. MATERIALS AND METHODS: Extensive database searches, including Web of Science, SciFinder, Google Scholar and China Knowledge Resource Integrated, were performed using keywords such as 'Thesium chinense', 'Bai Rui Cao', and their chemical constituents. In addition, local classic herbal literature on ethnopharmacology and relevant textbooks were consulted to provide a comprehensive survey of this ethnomedicine. RESULTS: Thirty four chemical constituents, including flavonoids, alkaloids, and terpenoids, have been identified from T. chinense. Of which, flavonoids are the predominant and characteristic constituents. The crude extracts, the purified constituents, and commercial available pharmaceutics have displayed diverse in vitro and in vivo pharmacological functions (e.g. anti-inflammation, antimicrobial activity, analgesic effect, hepaprotection), and are particularly useful as a potential therapeutic agent against inflammation-related diseases. CONCLUSIONS: T. chinense is an important ethnomedical medicine and possesses a satisfying effect for treating inflammation, microbial infection, and upper respiratory diseases. It has received plenty of researches on its phytochemical and pharmacological aspects since 1970s. These findings definitely establish the link between chemical composition and pharmacological application, and support the ethnomedical use of T. chinense in the indigenous medicine of China. However, chemical composition of this plant and the molecular mechanisms of purified constituents have not been comprehensively investigated, and thus the trace constituents and the therapeutic targets of bioactive constituents deserve a further exploration. Collectively, the researchers should pay more attention to a better understanding and application of this ethnomedical plant.

Spectrum-effect relationship between UPLC fingerprints and anti-lung cancer effect of Panax ginseng.

OBJECTIVES: Lung cancer has the highest mortality rate among the various types of cancer. Panax ginseng (C. A. Mey). is a popular anti-cancer herbal supplement. The quality control of ginseng is crucial to ensure its clinical efficacy. This study aimed to establish new quality control methods for ginseng and to identify its main active components responsible for lung cancer treatment. METHODS: Ultra-high-performance liquid chromatography (UPLC) was used to establish fingerprints of 18 batches of ginseng. CCK-8 test was performed to evaluate the inhibitory activity of ginseng on Lewis lung cancer (LLC) cells. The spectrum-effect relationship analysis of ginseng was assessed by canonical correlation analysis (CCA) and bioactivity validation. KEY FINDINGS: Six common peaks were identified and the variation coefficients were determined. The 18 batches of ginseng inhibited the proliferation of LLC cells to different degrees, showing different half maximal inhibitory concentration (IC50 ) values. Spectrum-effect relationship analysis showed that ginsenoside Ro is the main anti-proliferative constituent of LLC cell. CONCLUSIONS: Spectrum-effect relationship is suitable for quality control of ginseng used for lung cancer. It is also effective in discovering the active ingredients related to the clinical efficacy of traditional Chinese medicine.

Effects and mechanisms of scalp acupuncture on learning and memory in mice with lead poisoning.

OBJECTIVE: To study the effects and mechanism of scalp acupuncture on learning and memory ability in mice with lead poisoning. METHODS: From March 2018 to December 2018, 30 Kunming mice were randomly divided equally into the control group and the intervention group after intraperitoneal injection of lead acetate The intervention group received scalp acupuncture on the first day of the model establishment; the model group only received conventional feeding without treatment. At the same time, a control group of 15 rats was given the intraperitoneal injections of normal saline for 8 consecutive days, and only after routine feeding, no treatment was given. Determination of lead in blood was detected by Graphite Furnace Atomic Absorption Spectrometry, the Morris water maze test was used to detect the learning and memory function of mice, hydroxylamine colorimetric method was used to measure acetylcholinesterase (AChE) activity, and TUNEL staining was used to detect the apoptotic cells in the hippocampus. RESULTS: The results showed that the blood lead level of the model group (231.42±12.53µg/L) was significantly higher than that of the control group (20.43±4.62µg/L) (P<0.05); and there was no significant difference in blood lead content between the intervention group (228.12±5.21µg/L) and the model group. The Morris water maze test showed that from the fourth day of the orientation navigation experiment, the escape latency of the model group (22.2±4.10s) was longer than that of the control group (13.64±2.93s) (P<0.05); besides, from the third day, the escape latency of mice in the intervention group (13.52±9.18s) was significantly shortened compared with the model group (19.95±3.52s). In the space exploration experiment, in terms of passing through the platform, the distance (1.57±0.49m) and time (15.54±3.72s) of mice in the model group were longer than that of mice in the control group (0.73±0.44m, 3.24±2.24s) (P<0.05), the distance (0.41±0.28m) and time (3.0±1.93s) of mice in the intervention group were shorter than that of mice in the model group, and the difference was statistically significant (P<0.05). The apoptosis rate of hippocampus in the model group (8.79±0.37%) was significantly higher than that in the control group (3.56±0.44%) (P<0.05), and the apoptosis rate of hippocampus in the intervention group (4.36±0.12%0 was significantly lower than that in the model group (P<0.05). The expression of AchE in the model group (0.5±0.13U/ug) was significantly higher than that in the control group (0.23±0.04U/ug), but there was no significant difference in the AChE activity between the intervention group and the model group. CONCLUSIONS: In conclusion, scalp acupuncture can improve the learning and memory ability of mice with lead poisoning, and the decrease of hippocampal apoptotic cells may be a possible mechanism for the improvement of learning and memory function.

Determination of Oxyphylla A Enantiomers in the Fruits of Alpinia oxyphylla by a Chiral High-Performance Liquid Chromatography-Multiple Reaction Monitoring-Mass Spectrometry Method and Comparison of Their In Vivo Biological Activities.

(R)-Oxyphylla A, a natural product isolated from Alpinia oxyphylla Miquel as a food and medicinal plant, has been reported previously as a novel chiral compound that possesses a potential therapeutic value for Parkinson's disease (PD). A chiral high-performance liquid chromatography-multiple reaction monitoring-mass spectrometry method was developed to separate oxyphylla A enantiomers and to identify the presence of natural (S)-oxyphylla A for the first time. Twelve samples of dried A. oxyphylla fruits were analyzed in which a large variation in the abundance of enantiomers was observed. Moreover, (S)-oxyphylla A was less abundant in all tested samples, whereas fruits harvested from Hainan and Guangdong tended to have relatively higher total concentrations of enantiomers. Additionally, enantiomers exhibited comparable neuroprotective effects in the zebrafish model of PD without observed toxicity phenotype. The optimized enantioseparation method will be crucial for the quality control of A. oxyphylla and research on bioactivities facilitates the development of oxyphylla A as a potential therapeutic for neurodegenerative diseases.