Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

N-Cinnamoylpyrrole-derived alkaloids from the genus Piper as promising agents for ischemic stroke by targeting eEF1A1.

BACKGROUND: Ischemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile. PURPOSE: The present research aimed to explore the antineuroinflammatory and antioxidative stress effects of N-cinnamoylpyrrole-derived alkaloids isolated from the genus Piper and to explain the effects and mechanism on IS. METHODS: N-cinnamoylpyrrole-derived alkaloids were isolated from Piper boehmeriaefolium var. tonkinense and Piper sarmentosum and identified by various chromatographic methods. Lipopolysaccharide (LPS)-induced BV-2 microglia and a mouse model intracerebroventricularly injected with LPS were used to evaluate the antineuroinflammatory and antioxidative stress effects. Oxygen‒glucose deprivation/reperfusion (OGD/R) and transient middle cerebral artery occlusion (tMCAO) models were used to evaluate the effect of PB-1 on IS. To elucidate the fundamental mechanism, the functional target of PB-1 was identified by affinity-based protein profiling (ABPP) strategy and verified by cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and circular dichroism (CD) analyses. The effect of PB-1 on the NF-κB and NRF2 signaling pathways was subsequently evaluated via western blotting and immunofluorescence staining. RESULTS: The results showed that N-cinnamoylpyrrole-derived alkaloids significantly affected neuroinflammation and oxidative stress. The representative compound, PB-1 not only inhibited neuroinflammation and oxidative stress induced by LPS or OGD/R insult, but also alleviated cerebral ischemic injury induced by tMCAO. Further molecular mechanism research found that PB-1 promoted antineuroinflammatory and antioxidative stress activities via the NF-κB and NRF2 signaling pathways by targeting eEF1A1. CONCLUSION: Our research initially unveiled that the therapeutic impact of PB-1 on cerebral ischemic injury might rely on its ability to target eEF1A1, leading to antineuroinflammatory and antioxidative stress effects. The novel discovery highlights eEF1A1 as a potential target for IS treatment and shows that PB-1, as a lead compound that targets eEF1A1, may be a promising therapeutic agent for IS.

Eudesmane sesquiterpenoids with inhibitory effects on NO production from Artemisia princeps.

Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.

Three new phenolic glycosides and a new lignan glycoside from Gaultheria leucocarpa var. yunnanensis.

Three new phenolic glycosides (1-3) and a new lignan glycoside (4), together with five known compounds (5-9) were isolated from the ethanol extract of the aerial part of Gaultheria leucocarpa var. yunnanensis (Franch.) T.Z.Hsu & R.C.Fang. Their structures were determined on the basis of spectroscopic techniques, experimental and calculated ECD spectra, acid hydrolysis, and enzymatic hydrolysis experiments. All the isolates were evaluated for their anti-inflammatory and antioxidant activities. Compounds 7 and 8 exhibited inhibitory effects against the LPS-induced production of NO with IC50 of 63.71 and 10.66 µM, respectively, compared to L-NMMA having an IC50 of 6.95 µM. Besides, compound 7 also represented significant DPPH radical scavenging activity with EC50 of 18.75 µM, comparable with vitamin C (EC50 = 15.77 µM).

Melatonin Promotes Iron Reactivation and Reutilization in Peach Plants under Iron Deficiency.

The yellowing of leaves due to iron deficiency is a prevalent issue in peach production. Although the capacity of exogenous melatonin (MT) to promote iron uptake in peach plants has been demonstrated, its underlying mechanism remains ambiguous. This investigation was carried out to further study the effects of exogenous MT on the iron absorption and transport mechanisms of peach (Prunus persica) plants under iron-deficient conditions through transcriptome sequencing. Under both iron-deficient and iron-supplied conditions, MT increased the content of photosynthetic pigments in peach leaves and decreased the concentrations of pectin, hemicellulose, cell wall iron, pectin iron, and hemicellulose iron in peach plants to a certain extent. These effects stemmed from the inhibitory effect of MT on the polygalacturonase (PG), cellulase (Cx), phenylalanine ammonia-lyase (PAL), and cinnamoyl-coenzyme A reductase (CCR) activities, as well as the promotional effect of MT on the cinnamic acid-4-hydroxylase (C4H) activity, facilitating the reactivation of cell wall component iron. Additionally, MT increased the ferric-chelate reductase (FCR) activity and the contents of total and active iron in various organs of peach plants under iron-deficient and iron-supplied conditions. Transcriptome analysis revealed that the differentially expressed genes (DEGs) linked to iron metabolism in MT-treated peach plants were primarily enriched in the aminoacyl-tRNA biosynthesis pathway under iron-deficient conditions. Furthermore, MT influenced the expression levels of these DEGs, regulating cell wall metabolism, lignin metabolism, and iron translocation within peach plants. Overall, the application of exogenous MT promotes the reactivation and reutilization of iron in peach plants.

Transcriptome Profiles Reveal the Promoting Effects of Exogenous Melatonin on Fruit Softening of Chinese Plum.

In this study, we investigated the effect of exogenous melatonin (MT) on cell wall metabolism leading to Chinese plum (Prunus salicina Lindl.) fruit softening. Exogenous MT treatment increased the endogenous MT content in plum fruits before fruit ripening. However, in mature plum fruits, exogenous MT treatment decreased the fruit hardness, pulp hardness, fruit elasticity, contents of ion-bound pectin, covalently-bound pectin, hemicellulose, and cellulose, and activities of xyloglucan endotransglycosylase/hydrolase and endo-ß-1,4-glucanase, and increased the water-soluble pectin content, and activities of pectin methyl esterase, pectin lyase, polygalacturonase, ß-galactopyranosidase, and α-L-arabinofuranosidase. Transcriptome analysis revealed that the differentially expressed genes (DEGs) associated with cell wall metabolism in the exogenous MT-treated plum fruits were mainly enriched in the pentose and glucuronate interconversions, phenylpropanoid biosynthesis, cyanoamino acid metabolism, and galactose metabolism pathways. Analysis of these DEGs revealed that exogenous MT treatment affected the expression of genes regulating the cell wall metabolism. Overall, exogenous MT treatment promotes the fruit softening of Chinese plum.

Foegraecumoside O and P, a Pair of Triterpenoid Saponins with a 4/5/6 Fused Tricyclic Oleanane Carbon Skeleton from Lysimachia foenum-graecum Hance.

Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC50 at 12.4-19.2 µM in an MTT assay, comparing with the positive control doxorubicin, which had IC50 at 0.53-4.92 µM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed.

Chemical constituents from Acorus calamus with potent anti-diabetic and hepatoprotective activities.

Three previously undescribed compounds, (+)-7S,8S-syringoylglycerol-7-O-3',4'-dihydroxylphenylethanol (1), (+)-2S,3R-piscidic acid 1-methyl-5-ethyl ester (2), and 2'S-2-acetyl-3-(2,3-dihydroxypropoxyl)furan (3), together with one new natural product, 7S,8S-4,7,8-trihydroxyl-methyl phenylpropionate (4) and a known lignan (7S,8R)-methyl-4',7-epoxy-3,3'-dimethoxy-4,9-dihydroxylignan-9'-oate (5), were isolated from the ethanol extract of Acorus calamus Linn. rhizomes. Their structures were determined based on extensive spectroscopic analyses and computational methods. All the isolated compounds were evaluated for their in vitro GK activating and hepatoprotective activities, and compound 5 exhibited significant GK activating activity at 10-5 mol/L, compound 3 exhibited moderate protective effects to APAP-induced injuries of HepG2 cells at 10-5 mol/L. Furthermore, molecular docking of compound 5 bound with GK was carried out to investigate the possible structural insights into the potential binding patterns.

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

Loureirin C inhibits ferroptosis after cerebral ischemia reperfusion through regulation of the Nrf2 pathway in mice.

BACKGROUND: Ischemic stroke (IS) is considered as a serious cerebral vascular disease. Ferroptosis is a novel type of regulated cell death (RCD), that closely related to the occurrence and progress of IS. Loureirin C, a type of dihydrochalcone compound derived from the Chinese Dragon's blood (CDB). The effective components extracted from CDB have shown neuroprotective effects in ischemia reperfusion models. However, the role of Loureirin C in mice after IS is not well understood. Thus, it is worth to identify the effect and mechanism of Loureirin C on IS. PURPOSE: The present research aims to prove the existence of ferroptosis in IS and explore whether Loureirin C can inhibit ferroptosis by regulating nuclear factor E2 related factor 2 (Nrf2) pathway in mice and exert neuroprotective effects on IS models. METHODS: Middle cerebral artery occlusion and reperfusion (MCAO/R) model was established to evaluate the occurrence of ferroptosis and the potential Loureirin C brain-protective effect in vivo. The analysis of free iron, glutamate content, reactive oxygen species (ROS) and lipid peroxidation levels, along with transmission electron microscope (TEM) was applied to prove the existence of ferroptosis. The function of Loureirin C on Nrf2 nuclear translocation was verified by immunofluorescence staining. In vitro, primary neurons and SH-SY5Y cells were processed with Loureirin C after oxygen and glucose deprivation-reperfusion (OGD/R). ELISA kits, western blotting, co-immunoprecipitation (Co-IP) analysis, immunofluorescence, and quantitative real-time PCR were devoted to proving the neuroprotective effects of Loureirin C on IS via regulating ferroptosis and Nrf2 pathways. RESULTS: The results showed that Loureirin C not only dramatically alleviated brain injury and inhibited neurons ferroptosis in mice after MCAO/R, but also dose-dependently reduce ROS accumulation in ferroptosis after OGD/R. Further, Loureirin C inhibits ferroptosis by activating Nrf2 pathway, and promoting nuclear translocation of Nrf2. Besides, Loureirin C increases heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) and glutathione peroxidase 4 (GPX4) content after IS. Intriguingly, the anti-ferroptosis effect of Loureirin C is weakened by Nrf2 knockdown. CONCLUSION: Our discoveries first revealed that the inhibitory action of Loureirin C on ferroptosis may greatly depend on its adjusting effect on the Nrf2 pathway, suggesting that Loureirin C could act as a novel anti-ferroptosis candidate and play a therapeutic role in IS. These novel discoveries on the role of Loureirin C on IS models reveal an innovative method that may contribute to neuroprotection for the prevention of IS.

Prediction Model of Treatment Effect of Anlotinib on Extensive-stage Small Cell Lung Cancer Based on Combination of Disease and Syndrome Information / 肿瘤防治研究

Objective To construct a nomogram prediction model for the treatment effect of anlotinib with the participation of traditional Chinese medicine syndrome elements on the patients with extensive-stage small cell lung cancer (ES-SCLC) who previously received multiple lines of chemotherapy. Methods The clinical data of 127 patients with ES-SCLC who received at least two cycles of anlotinib treatment were retrospectively studied. Kaplan-Meier method was used to analyze the relationship between each factor and the overall survival time. Cox regression analysis was applied to screen the independent influencing factors of the prognosis of patients with ES-SCLC. R language was employed to build a nomogram prediction model, C-index was used to evaluate the model, and calibration curve was adopted to verify the accuracy of the model. Results Age, PS score, brain metastases, qi deficiency syndrome, yin deficiency syndrome, and blood stasis syndrome were related risk factors for ES-SCLC treated with anlotinib. PS score, brain metastasis, and blood stasis syndrome were independent prognostic factors. On the basis of these three independent influencing factors, a nomogram model was established to predict the prognosis of patients with ES-SCLC treated with anlotinib. The predicted risk was close to the actual risk, showing a high degree of coincidence. Conclusion The nomogram model established with PS score, blood stasis syndrome elements, and brain metastasis as independent factors can predict the prognosis of patients with ES-SCLC receiving second- and third-line treatment of anlotinib.

Construction and Validation of A Predictive Model Including TCM Pathogenic Syndrome for Short-term Efficacy of PD-1 Inhibitors in Advanced Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer.

Melatonin and arbuscular mycorrhizal fungi synergistically improve drought toleration in kiwifruit seedlings by increasing mycorrhizal colonization and nutrient uptake.

Kiwifruit is a vine fruit tree that is vulnerable to water deficiency due to its shallow root system and large leaves. Although mycorrhizal inoculation and melatonin application has been proved to improve plants drought tolerance, their interaction effects are still unclear. In this study, arbuscular mycorrhizal (AM) fungi incubation and melatonin (MT) irrigation were applied to kiwifruit seedlings alone or in combination to investigate their effect on drought tolerance. The results revealed that AM had more effect on promoting root biomass, water use efficiency, and uptake of nitrogen, phosphorus and iron. While MT was more effective in promoting shoot biomass and antioxidant enzyme activities to remove reactive oxygen species accumulation. Moreover, MT supplementary significantly increased the AM colonization, spore density and hyphal length density in roots. Therefore, combined application of AM fungi and MT had additive effects on improvement biomass accumulation, increasing chlorophyll content, photosynthetic efficiency, catalase activity, and decreasing malondialdehyde accumulation under drought stress, thus promoting plant growth and alleviating the drought damage to plant. These results provide guidance for AM and MT combined application to improve abiotic resistance in plants.

Lignans and terpenoids from Gaultheria leucocarpa var. yunnanensis and their anti-inflammatory and antioxidant activities.

Six new compounds, including three lignans (1a, 1b, and 2), two abietane-type diterpenoids (3 and 4), and a triterpenoid (5), together with 13 known compounds (6a, 6b, and 7-17) were isolated from the aerial parts of Gaultheria leucocarpa var. yunnanensis. Their structures were elucidated by analysis of spectroscopic data involving NMR, IR, UV, and HRESIMS. The absolute configurations of lignans were confirmed by experimental and calculated ECD spectra. The anti-inflammatory and antioxidant activities of the isolates were evaluated. Compounds 12, 13, and 15 showed inhibitory effects against the LPS-induced production of NO in BV-2 microglial cells with the IC50 values of 30.50, 23.26, and 13.02 µM, respectively. In addition, compounds 2 and 7 performed moderate DPPH radical scavenging activities.

Loureirin C ameliorates ischemia and reperfusion injury in rats by inhibiting the activation of the TLR4/NF-κB pathway and promoting TLR4 degradation.

Ischemic stroke is a leading cause of death and disability worldwide. Post-ischemia, microglia respond immediately to the alternations in neuronal activity and mediate inflammation. Toll-like receptor 4 (TLR4) plays a key role in this phenomenon. To explore the effect of loureirin C, an effective compound from Chinese Dragon's blood, on ischemic stroke, Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) with/without intragastric administration of loureirin C (7, 14, and 28 mg/kg). Loureirin C alleviated MCAO/R-induced brain impairment evaluated by neurological scores (p < 0.001), brain water content (p < 0.001), and cerebral infarct volume (p = 0.001). The neuroprotective (p < 0.001) and inhibitory effects on microglial activation (p < 0.001) of loureirin C were revealed by immunofluorescence. Rescue studies with TLR4 overexpression in BV-2 microglia showed that the antiinflammatory effect of loureirin C was attributable to the inhibition of TLR4 protein expression. Moreover, co-immunoprecipitation assays showed that the binding of Triad3A, an E3 ubiquitin ligase of TLR4, was increased by loureirin C (p = 0.003). Our study demonstrates that loureirin C could be a promising therapeutic agent for the management of ischemic stroke by inhibiting microglial activation, potentially by Triad3A-mediated promotion of TLR4 ubiquitination and degradation.

Ultra-HPLC-MS pseudo-targeted metabolomic profiling reveals metabolites and associated metabolic pathway alterations in Asian plum (Prunus salicina) fruits in response to gummosis disease.

Plum (Prunus spp.) is an economically and nutritionally important stone fruit that is grown worldwide. Gummosis disease (GD) is one of the most common limiting factors that adversely affects the yield and quality of stone fruits such as plum. Elucidating plum fruit metabolomics responses is essential to develop sustainable agricultural practices to combat GD in the future. Herein, an ultra-high-performance liquid chromatography coupled to mass-spectrometry (UHPLC-MS) pseudo-targeted metabolomic profiling was first performed to elucidate the overall metabolic alterations in Asian plum (Prunus salicina Lindl.) fruit in response to GD. The most pivotal differential metabolites, including certain amino acids and proanthocyanidins, in GD and control groups were identified by combining multivariate data analysis with strict statistical criteria. Metabolic pathway enrichment analysis showed that GD induced a series of coordinated defence responses and reprogramming of various metabolic pathways, including glucosinolate biosynthesis, 2-oxocarboxylic acid metabolism, valine, leucine and isoleucine degradation, and isoquinoline alkaloid biosynthesis pathways. Using UHPLC-MS-based pseudo-targeted metabolomic profiling, we systematically evaluated overall metabolic modifications in Asian plum fruits in response to GD for the first time. The identified metabolic pathway alterations helped to better understand the internal relationships and related metabolic networks.

Four New Sesquiterpenoids from Zanthoxylum nitidum.

Zanthoxylum nitidum (Roxb.) DC., is one of Guangxi's characteristic national medicines, and is the classic Laoban medicine of Yao people "Ru Shan Hu" and Zhuang medicine "Liang Bei Zhen". It has been used as an anti-inflammatory, analgesic and haemostatic medicine for thousands of years. In this study, four new sesquiterpenoids (1-4), along with six previously described coumarins (5-10), were isolated from 95 % EtOH extract of Zanthoxylum nitidum. Comprehensive spectroscopic analyses (NMR and HR-ESI-MS) were used to elucidate the structures of these isolates. The absolute configurations of nitidumine A-D (1-4) were established by electronic circular dichroism (ECD). Their cytotoxicity of all the isolates against five cancer cell lines (T24, HeLa, MGC-803, A549, and HepG2) was evaluated by MTT experiment and found not to be cytotoxicity.

Lignanamides from the stems of Piper hancei maxim. and their anti-inflammatory and cytotoxic activities.

Four new lignanamides, hancamides A - D (1-4), together with four known analogs (5-8), were isolated from the stems of Piper hancei Maxim. Their structures were determined based on 1D and 2D NMR, IR, UV, and HR-ESIMS spectroscopic analysis as well as by comparison with the reported data. All the isolates exhibited potential inhibitory effects on NO production in LPS-induced BV-2 microglial cells, with IC50 values of 4.26-40.68 µM. Moreover, compounds 2 and 8 displayed moderate cytotoxic activities against MGC-803, HepG2, SKOV-3, T24, and HeLa cells, with IC50 values ranging from 13.57 to 34.20 µM, respectively.

Spectrum-Effect Relationship Analysis of Bioactive Compounds in Zanthoxylum nitidum (Roxb.) DC. by Ultra-High Performance Liquid Chromatography Mass Spectrometry Coupled With Comprehensive Filtering Approaches.

Zanthoxylum nitidum (Roxb.) DC. (ZN), with strong effects of anti-inflammation and antioxidant activities is treated as a core herb in traditional Chinese medicine (TCM) preparation for treating stomachache, toothache, and rheumatoid arthritis. However, the active ingredients of ZN are not fully clarified due to its chemical complexity. In the present study, a double spectrum-effect analysis strategy was developed and applied to explore the bioactive components in herbs, and ZN was used as an example. Here, the chemical components in ZN were rapidly and comprehensively profiled based on the mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension approaches. Furthermore, the fingerprints of 20 batches of ZN samples were analyzed by high-performance liquid chromatography, and the anti-inflammatory and antioxidant activities of the 20 batches of ZN samples were studied. Finally, the partial least squares regression (PLSR), gray relational analysis models, and Spearman's rank correlation coefficient (SRCC) were applied to discover the bioactive compounds in ZN. As a result, a total of 48 compounds were identified or tentatively characterized in ZN, including 35 alkaloids, seven coumarins, three phenolic acids, two flavonoids, and one lignan. The results achieved by three prediction models indicated that peaks 4, 12, and 17 were the potential anti-inflammatory compounds in ZN, whereas peaks 3, 5, 7, 12, and 13 were involved in the antioxidant activity. Among them, peaks 4, 5, 7, and 12 were identified as nitidine, chelerythrine, hesperidin, and oxynitidine by comparison with the standards and other references. The data in the current study achieved by double spectrum-effect analysis strategy had great importance to improve the quality standardization of ZN, and the method might be an efficiency tool for the discovery of active components in a complex system, such as TCMs.

Detection and identification of tea leaf diseases based on AX-RetinaNet.

The accurate detection and identification of tea leaf diseases are conducive to its precise prevention and control. Convolutional neural network (CNN) can automatically extract the features of diseased tea leaves in the images. However, tea leaf images taken in natural environments have problems, such as complex backgrounds, dense leaves, and large-scale changes. The existing CNNs have low accuracy in detecting and identifying tea leaf diseases. This study proposes an improved RetinaNet target detection and identification network, AX-RetinaNet, which is used for the automatic detection and identification of tea leaf diseases in natural scene images. AX-RetinaNet uses an improved multiscale feature fusion module of the X-module and adds a channel attention module, Attention. The feature fusion module of the X-module obtains feature maps with rich information through multiple fusions of multi-scale features. The attention module assigns a network adaptively optimized weight to each feature map channel so that the network can select more effective features and reduce the interference of redundant features. This study also uses data augmentation methods to solve the problem of insufficient samples. Experimental results show the detection and identification accuracy of AX-RetinaNet for tea leaf diseases in natural scene images is better than the existing target detection and identification networks, such as SSD, RetinaNet, YOLO-v3, YOLO-v4, Centernet, M2det, and EfficientNet. The AX-RetinaNet detection and identification results indicated the mAP value of 93.83% and the F1-score value of 0.954. Compared with the original network, the mAP value, recall value, and identification accuracy increased by nearly 4%, by 4%, and by nearly 1.5%, respectively.