A review of botany, phytochemistry, pharmacology, and applications of the herb with the homology of medicine and food: Ligustrum lucidum W.T. Aiton.

Ligustrum lucidum W.T. Aiton is an outstanding herb with the homology of medicine and food. Its ripe fruits are traditionally used as an important tonic for kidneys and liver in China. Ligustrum lucidum W.T. Aiton is rich in nutritional components and a variety of bioactive ingredients. A total of 206 compounds have been isolated and identified, they mainly include flavonoids, phenylpropanoids, iridoid glycosides, and triterpenoids. These compounds exert anti-osteoporosis, anti-tumor, liver protective, antioxidant, anti-inflammatory, and immunomodulatory effects. Ligustrum lucidum W.T. Aiton has been traditionally used to treat many complex diseases, including osteoporotic bone pain, rheumatic bone, cancer, related aging symptoms, and so on. In the 2020 Edition of Chinese Pharmacopoeia, there are more than 100 prescriptions containing L. lucidum W.T. Aiton. Among them, some classical preparations including Er Zhi Wan and Zhenqi fuzheng formula, are used in the treatment of various cancers with good therapeutic effects. Additionally, L. lucidum W.T. Aiton has also many excellent applications for functional food, ornamental plants, bioindicator of air pollution, algicidal agents, and feed additives. Ligustrum lucidum W.T. Aiton has rich plant resources. However, the application potential of it has not been fully exploited. We hope that this paper provides a theoretical basis for the high-value and high-connotation development of L. lucidum W.T. Aiton in the future.

Ganoderma lucidum spore extract improves sleep disturbances in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer's disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats. Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot. Results: Treatment with 720 mg/kg RGLS for 14 days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN). Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.

Sporoderm-removed Ganoderma lucidum spores ameliorated early depression-like behavior in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer's disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer's disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear. Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test. Results: Behavioral tests demonstrated that RGLS (360 and 720 mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC. Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.

Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ sensitivity.

Glioma is one of the most common primary malignant tumors of the central nervous system. Temozolomide (TMZ) is the only effective chemotherapeutic agent, but it easily develops resistance and has unsatisfactory efficacy. Consequently, there is an urgent need to develop safe and effective compounds for glioma treatment. The cytotoxicity of 30 candidate compounds to glioma cells was detected by the CCK-8 assay. Daurisoline (DAS) was selected for further investigation due to its potent anti-glioma effects. Our study revealed that DAS induced glioma cell apoptosis through increasing caspase-3/6/9 activity. DAS significantly inhibited the proliferation of glioma cells by inducing G1-phase cell cycle arrest. Meanwhile, DAS remarkably suppressed the migration and invasion of glioma cells by regulating epithelial-mesenchymal transition. Mechanistically, our results revealed that DAS impaired the autophagic flux of glioma cells at a late stage by mediating the PI3K/AKT/mTOR pathway. DAS could inhibit TMZ-induced autophagy and then significantly promote TMZ chemosensitivity. Nude mice xenograft model revealed that DAS could restrain glioma proliferation and promote TMZ chemosensitivity. Thus, DAS is a potential anti-glioma drug that can improve glioma sensitivity to TMZ and provide a new therapeutic strategy for glioma in chemoresistance.

Constituents, pharmacological activities, pharmacokinetic studies, clinical applications, and safety profile on the classical prescription Kaixinsan.

Kaixinsan (KXS) is a noteworthy classical prescription, which consists of four Chinese medicinal herbs, namely Polygalae Radix, Ginseng Radix et Rhizoma, Poria, and Acori Tatarinowii Rhizoma. KXS was initially documented in the Chinese ancient book Beiji Qianjin Yaofang written by Sun Simiao of the Tang Dynasty in 652 A.D. As a traditional Chinese medicine (TCM) prescription, it functions to nourish the heart and replenish Qi, calm the heart tranquilize the mind, and excrete dampness. Originally used to treat amnesia, it is now also effective in memory decline and applied to depression. Although there remains an abundance of literature investigating KXS from multiple aspects, few reviews summarize the features and research, which impedes better exploration and exploitation of KXS. This article intends to comprehensively analyze and summarize up-to-date information concerning the chemical constituents, pharmacology, pharmacokinetics, clinical applications, and safety of KXS based on the scientific literature, as well as to examine possible scientific gaps in current research and tackle issues in the next step. The chemical constituents of KXS primarily consist of saponins, xanthones, oligosaccharide esters, triterpenoids, volatile oils, and flavonoids. Of these, saponins are the predominant active ingredients, and increasing evidence has indicated that they exert therapeutic properties against mental disease. Pharmacokinetic research has illustrated that the crucial exposed substances in rat plasma after KXS administration are ginsenoside Re (GRe), ginsenoside Rb1 (GRb1), and polygalaxanthone III (POL). This article provides additional descriptions of the safety. In this review, current issues are highlighted to guide further comprehensive research of KXS and other classical prescriptions.

Remimazolam attenuates myocardial ischemia-reperfusion injury by inhibiting the NF-ĸB pathway of macrophage inflammation.

BACKGROUND: Inflammation is a major contributing factor in myocardial ischemia/reperfusion (I/R) injury, and targeting macrophage inflammation is an effective strategy for myocardial I/R therapy. Though remimazolam is approved for sedation, induction, and the maintenance of general anesthesia in cardiac surgery, its effect on cardiac function during the perioperative period has not been reported. Therefore, this research aimed to explore the impact of remimazolam on inflammation during myocardial ischemia/reperfusion (I/R) injury. METHODS: An in vivo myocardial I/R mice model and an in vitro macrophage inflammation model were used to confirm remimazolam's cardiac protective effect. In vivo, we used echocardiography, hematoxylin and eosin (HE), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine remimazolam's therapeutic effects on myocardial I/R injury and inflammation. In vitro, we employed enzyme-linked immunosorbent assay (ELISA), Western blot, Real-time Quantitative PCR (qPCR), flow cytometry, and immunofluorescence staining to assess inflammatory responses, especially remimazolam's effects on macrophage polarization after I/R. Furthermore, molecular docking was used to identify its potential binding targets on the inflammatory pathway to explore the mechanism of remimazolam. RESULTS: Remimazolam exhibited significant anti-myocardial I/R injury activity by inhibiting macrophage-mediated inflammation to reduce myocardial infarction, enhancing cardiac function. In addition, macrophage depletion counteracted improved cardiac function by remimazolam treatment. Mechanistically, the activated NF-ĸB signaling pathway and phosphorylation of p50 and p65 were repressed for anti-inflammatory effect. Consistently, two binding sites on p50 and p65 were identified by molecular docking to affect their phosphorylation of the Ser, Arg, Asp, and His residues, thus regulating NF-κB pathway activity. CONCLUSION: Our results unveil the therapeutic potential of remimazolam against myocardial I/R injury by inhibiting macrophages polarizing into the M1 type, alleviating inflammation.

Discrimination of Maturity Stages of Cabernet Sauvignon Wine Grapes Using Visible-Near-Infrared Spectroscopy.

Grape quality and ripeness play a crucial role in producing exceptional wines with high-value characteristics, which requires an effective assessment of grape ripeness. The primary purpose of this research is to explore the possible application of visible-near-infrared spectral (Vis-NIR) technology for classifying the maturity stages of wine grapes based on quality indicators. The reflection spectra of Cabernet Sauvignon grapes were recorded using a spectrometer in the spectral range of 400 nm to 1029 nm. After measuring the soluble solids content (SSC), total acids (TA), total phenols (TP), and tannins (TN), the grape samples were categorized into five maturity stages using a spectral clustering method. A traditional supervised classification method, a support vector machine (SVM), and two deep learning techniques, namely stacked autoencoders (SAE) and one-dimensional convolutional neural networks (1D-CNN), were employed to construct a discriminant model and investigate the association linking grape maturity stages and the spectral responses. The spectral data went through three commonly used preprocessing methods, and feature wavelengths were extracted using a competitive adaptive reweighting algorithm (CARS). The spectral data model preprocessed via multiplicative scattering correction (MSC) outperformed the other two preprocessing methods. After preprocessing, a comparison was made between the discriminant models established with full and effective spectral data. It was observed that the SAE model, utilizing the feature spectrum, demonstrated superior overall performance. The classification accuracies of the calibration and prediction sets were 100% and 94%, respectively. This study showcased the dependability of combining Vis-NIR spectroscopy with deep learning methods for rapidly and accurately distinguishing the ripeness stage of grapes. It has significant implications for future applications in wine production and the development of optoelectronic instruments tailored to the specific needs of the winemaking industry.

Medication and prescription rules for treating spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary / 数字中医药（英文）

@#【Objective】   To explore the prescriptions related to the treatment of spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary (Tai Ping Hui Min He Ji Ju Fang,《太平惠民和剂局方》, TPHMHJJF), and investigate the medication and prescription rules. 【Methods】   The prescriptions of TPHMHJJF for treating spleen and stomach diseases were screened, and the data set was established by entering the prescriptions and standardized drug names using WPS Excel 2019. Herb frequency statistics, efficacy categorization, property, flavor, meridian tropism, association rules, cluster analysis, factor analysis, and complex network analysis were performed using Python 3.6.8 programming language and Gephi 0.9.2 visualization software. 【Results】   A total of 239 prescriptions were included after the screening, and the dosage forms were mainly pills and powders. The study involved 200 herbal medicines, among which 40 herbs had a frequency of ≥ 12. The herb with the highest frequency was Ganjiang (Zingiber Rhizoma). The herb properties were mainly warm in nature, with the most pungent herbs. Most herbs were attributed to the spleen and stomach meridians, and tonifying medicine were the main species. The association rule analysis identified 26 second-order association rules and 16 third-order association rules, with "Renshen (Ginseng Radix et Rhizoma) → Fuling (Poria)" as the leading rule in the former and "Fuling (Poria) + Baizhu (Atractylodis Macrocephalae Rhizome) → Renshen (Ginseng Radix et Rhizoma)" as the leading rule in the latter. Also, cluster analysis divided the top 30 herbs into six herb combinations that can warm the middle, move Qi, and dry dampness effectively. Factor analysis extracted 13 common factors, with Renshen (Ginseng Radix et Rhizoma), Fuling (Poria), and Baizhu (Atractylodis Macrocephalae Rhizome) as the highest contributing factors. Lastly, complex network analysis yielded the core prescription of 14 herbs, with Ganjiang (Zingiber Rhizoma), Renshen (Ginseng Radix et Rhizoma), Gancao (Glycyrrhizae Radix et Rhizome), and Chenpi (Citri Reticulatae Pericarpium) among the herbs with a higher weighting degree. 【Conclusion】  TPHMHJJF is mainly based on the use of warming herbs to treat spleen and stomach diseases, and its medication rule can be summarized into three aspects: (i) primarily using warming and tonifying to warm the middle and dissipate cold, (ii) using the method of moving Qi with aromatic nature to delight the spleen and appetize the stomach, and (iii) emphasizing the regulation of Qi and blood to calm the five zang-organs.