Characteristics and comparative study of medicinal materials between China and India based on data mining from literatures.

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.

LC-MS based metabonomics study on protective mechanism of ESWW in cerebral ischemia via CYTC/Apaf-1/NDRG4 pathway.

BACKGROUND: Ershiwuwei Zhenzhu pills was originally recorded in the Tibetan medical book Si Bu Yi Dian in the 8th century AD and is now included in the Pharmacopoeia of the People's Republic of China (2020). The pills can calm the nerves and open the mind as well as treat cerebral ischemia reperfusion injury, stroke, hemiplegia. However, its quality standards have not yet been established, and the therapeutic effect on cerebral ischemia by regulating the mitochondrial apoptosis pathway has not been elucidated. STUDY DESIGN AND METHODS: LC-MS was used to establish quality standards for Ershiwuwei Zhenzhu pills. Metabonomics, molecular docking, neuroethology, cerebral infarction ratio, pathological detection of diencephalon, cortex, and hippocampus, and molecular biology techniques were used to reveal the mechanism of the pills in regulating the mitochondrial apoptosis pathway to treat cerebral ischemia. RESULTS: The contents of 20 chemical components in Ershiwuwei Zhenzhu pills from 12 batches and 8 manufacturers was determined for the first time. Eleven differential metabolites and three metabolic pathways, namely, fructose and mannose metabolism, glycerophospholipid metabolism, and purine metabolism, were identified by metabonomics. The pills improved the neuroethology abnormalities of MCAO rats and the pathological damage in the diencephalon and decreased the ratio of cerebral infarction. It also significantly reduced the mRNA expression of AIF, Apaf-1, cleared caspase8, CytC, and P53 mRNA in the brain tissue and the protein expression of Apaf-1 and CYTC and increased the protein expression of NDRG4. CONCLUSION: In vitro quantitative analysis of the in vitro chemical components of Ershiwuwei Zhenzhu pills has laid the foundation for improving its quality control. The potential mechanism of the pills in treating cerebral ischemia may be related to the Apaf-1/CYTC/NDRG4 apoptosis pathway. This work provides guidance for clinical drug use for patients.

Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules.

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling. Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored. Methods: Ultra-performance liquid chromatography-tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models. Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue. Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.

The study of chemical components in Qishiwei Zhenzhu pills and its anti-apoptotic mechanism in cerebral ischemic based on LC-MS and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishiwei Zhenzhu pills are one of the most representative precious treasure proprietary medicines and have been used for nearly 500 years in clinical practice in Chinese. This medicine can prevent diseases and play a certain role in fighting altitude sickness with cerebral ischemia. AIM OF THE STUDY: This study used LC-MS to analyse the chemical constituents of Qishiwei Zhenzhu pills, which laid a foundation for the improvement of the quality standard and the basic research of pharmacodynamics substances. This study aims to reveal the mechanism of Qishiwei Zhenzhu pills on cerebral ischemia from the perspective of the inflammatory and apoptotic pathway. MATERIALS AND METHOD: UPLC-Q-TOF-MS was used to analyse the chemical constituents of Qishiwei Zhenzhu pills qualitatively. HPLC-QQQ-MS was used to analyse the contents of Qishiwei Zhenzhu pills quantitatively. The therapeutic target and pathway of Qishiwei Zhenzhu pills in the treatment of ischemic stroke were predicted on the basis of network pharmacology. On the basis of the MCAO rat model, the cerebral infarction rate (TTC staining) and the number of Nissl bodies (toluidine blue staining) were measured, the pathological morphologies of cortex and hippocampus were observed (HE staining), and the mRNA levels were determined by RT-PCR. The protein expressions of Bax, Bcl-2, and Caspase3 in the ischemic brain tissue of rats were determined using the WB method. RESULTS: A total of 42 chemical constituents, including 11 triterpenoids, 10 flavonoids, 8 organic acids and their derivatives, 4 diterpenoids, 4 tannins, 2 steroids, and 3 other components, were identified from Qishiwei Zhenzhu pills by UPLC-Q-TOF-MS. HPLC-QQQ-MS results found that among the 16 different batches, the content difference between the two batches of preparations with the national drug approval number was small and that the quality was stable. However, significant differences were observed among the preparations of nine medical institutions. Network pharmacology study found that the effect of Qishiwei Zhenzhu pills might be related to the AGE-rage and tumour necrosis factor signalling pathways. Qishiwei Zhenzhu pills could improve the neurobehavioral abnormalities of MCAO rats, reduce the rate of cerebral infarction, improve the pathological changes in the hippocampal area of brain tissue, and increase the number of Nissl body in the brain tissue. Qishiwei Zhenzhu pills tended to reduce the mRNA transcription levels of Bax, Caspase-3, p65, c-fos and VEGF-A and increase the expression of Bcl-2 and MAPK8 mRNA. Moreover, the Bax protein expression tended to decrease, and the bcl-2 protein expression tended to increase. CONCLUSIONS: A total of 42 chemical components were qualitatively identified from Qishiwei Zhenzhu pills, and 16 chemical components from 16 batches were determined. These components improved the quality standard level of Qishiwei Zhenzhu pills and provided reference for the later exploration of its pharmacodynamics substance basis. The protective mechanism of Qishiwei Zhenzhu pills against ischemic stroke might be related to the downregulation of the apoptosis factor caspase-3.

The application and sustainable development of coral in traditional medicine and its chemical composition, pharmacology, toxicology, and clinical research.

This review discusses the variety, chemical composition, pharmacological effects, toxicology, and clinical research of corals used in traditional medicine in the past two decades. At present, several types of medicinal coral resources are identified, which are used in 56 formulas such as traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uyghur medicine. A total of 34 families and 99 genera of corals are involved in medical research, with the Alcyoniidae family and Sarcophyton genus being the main research objects. Based on the structural types of compounds and the families and genera of corals, this review summarizes the compounds primarily reported during the period, including terpenoids, steroids, nitrogen-containing compounds, and other terpenoids dominated by sesquiterpene and diterpenes. The biological activities of coral include cytotoxicity (antitumor and anticancer), anti-inflammatory, analgesic, antibacterial, antiviral, immunosuppressive, antioxidant, and neurological properties, and a detailed summary of the mechanisms underlying these activities or related targets is provided. Coral toxicity mostly occurs in the marine ornamental soft coral Zoanthidae family, with palytoxin as the main toxic compound. In addition, nonpeptide neurotoxins are extracted from aquatic corals. The compatibility of coral-related preparations did not show significant acute toxicity, but if used for a long time, it will still cause toxicity to the liver, kidneys, lungs, and other internal organs in a dose-dependent manner. In clinical applications, individual application of coral is often used as a substitute for orthopedic materials to treat diseases such as bone defects and bone hyperplasia. Second, coral is primarily available in the form of compound preparations, such as Ershiwuwei Shanhu pills and Shanhu Qishiwei pills, which are widely used in the treatment of neurological diseases such as migraine, primary headache, epilepsy, cerebral infarction, hypertension, and other cardiovascular and cerebrovascular diseases. It is undeniable that the effectiveness of coral research has exacerbated the endangered status of corals. Therefore, there should be no distinction between the advantages and disadvantages of listed endangered species, and it is imperative to completely prohibit their use and provide equal protection to help them recover to their normal numbers. This article can provide some reference for research on coral chemical composition, biological activity, chemical ecology, and the discovery of marine drug lead compounds. At the same time, it calls for people to protect endangered corals from the perspectives of prohibition, substitution, and synthesis.

The application of mirabilite in traditional Chinese medicine and its chemical constituents, processing methods, pharmacology, toxicology and clinical research.

Purpose: This study reviews the use of mirabilite in traditional Chinese medicine and various preparations by describing its chemical composition, processing methods, pharmacology, toxicology, and clinical research progress. Methods: The applications and processing methods of mirabilite are searched in traditional and modern Chinese medical writings, and the articles on chemical composition, pharmacological effects, toxicology, and clinical studies of mirabilite and its combinations in PubMed and China Knowledge Network are reviewed, sorted, and analyzed. Results: The main chemical component of mirabilite is sodium sulfate decahydrate (Na2SO4·10H2O), followed by small amounts of sodium chloride, magnesium sulfate, calcium sulfate, and other inorganic salts. This study systematically organizes the history of the medicinal use of mirabilite in China for more than 2,000 years. This mineral has been used by nine Chinese ethnic groups (Han, Dai, Kazakh, Manchu, Mongolian, Tujia, Wei, Yi, and Tibetan) in a large number of prescription preparations. The Pharmacopoeia of the People's Republic of China (2020 edition) records stated that mirabilite can be used for abdominal distension, abdominal pain, constipation, intestinal carbuncle, external treatment of breast carbuncle, hemorrhoids, and other diseases. The traditional processing methods of mirabilite in China include refining, boiling, sautéing, filtration after hot water blistering, and firing. Since the Ming Dynasty, processing by radish has become the mainstream prepared method of mirabilite. Mirabilite can exhibit anti-inflammatory detumescence effects by inhibiting AMS, LPS, IL-6, IL-10, TNF-α, and NO levels and attenuating the upregulation of TNF-α and NF-κB genes. It can promote cell proliferation and wound healing by increasing the production of cytokines TGFß1 and VEGF-A and gastrointestinal motility by increasing the release of vasoactive intestinal peptide, substance P, and motilin. It can increase the expression of low-density lipoprotein receptor and AKT phosphorylation in the liver by up-regulating bile acid synthesis genes; reduce TRB3 expression in the liver, FGF15 co-receptor KLB expression, and FGF15 production in the ileum, and JNK signal transduction; and increase the transcription of CYP7A1 to achieve a cholesterol-lowering effect. Mirabilite also has a variety of pharmacological effects, such as regulating intestinal flora, anti-muscle paralysis, anti-colon cancer, promoting water discharge, and analgesic. Only a few toxicological studies on mirabilite are available. External application of mirabilite can cause local skin to be flushed or itchy, and its oral administration is toxic to neuromuscular cells. The sulfur ions of its metabolites can also be toxic to the human body. At present, no pharmacokinetic study has been conducted on mirabilite as a single drug. This mineral has been widely used in the clinical treatment of inflammation, edema, wound healing, digestive system diseases, infusion extravasation, hemorrhoids, skin diseases, breast accumulation, muscle paralysis, intestinal preparation before microscopic examination, and other diseases and symptoms. Conclusion: Mirabilite has good application prospects in traditional Chinese medicine and ethnomedicine. In-depth research on its processing methods, active ingredients, quality control, pharmacokinetics, pharmacological and toxicological mechanisms, and standardized clinical application is needed. This paper provides a reference for the application and research of mirabilite in the future.

The Application of Pearls in Traditional Medicine of China and Their Chemical Constituents, Pharmacology, Toxicology, and Clinical Research.

Although pearls are well known by most people, their medicinal value has not been popularized. This article collates the medicinal history of pearls over 2,000 years in China, including the application of pearls in the traditional medicine of China and their various preparations, as well as the progress of their chemical constituents, pharmacology, toxicology, and clinical research. Pearls from three different sources are used as medical materiel by 9 nationalities and 251 prescription preparations in China. In addition, pearls contain various inorganic constituents, such as calcium carbonate, trace elements, and water, and organic constituents, such as amino acids. In terms of pharmacology, pearls have many effects such as calming, improving cognitive ability, being anti-epileptic, promoting bone growth and regeneration, promoting the proliferation and migration of human microvascular endothelial cells, protecting the heart, anti-hemolysis, and anti-oxidation. In terms of toxicology, pearls are safe to take for a long time without exerting obvious adverse reactions. In terms of clinical application, pearls have been used to treat many diseases and conditions, such as convulsions, epilepsy, palpitations, eye diseases, ulcer diseases, skin diseases, or skin lesions. This article provides a reference for the application and research of pearls in the future.

Discovery of Epipodophyllotoxin-Derived B2 as Promising XooFtsZ Inhibitor for Controlling Bacterial Cell Division: Structure-Based Virtual Screening, Synthesis, and SAR Study.

The emergence of phytopathogenic bacteria resistant to antibacterial agents has rendered previously manageable plant diseases intractable, highlighting the need for safe and environmentally responsible agrochemicals. Inhibition of bacterial cell division by targeting bacterial cell division protein FtsZ has been proposed as a promising strategy for developing novel antibacterial agents. We previously identified 4'-demethylepipodophyllotoxin (DMEP), a naturally occurring substance isolated from the barberry species Dysosma versipellis, as a novel chemical scaffold for the development of inhibitors of FtsZ from the rice blight pathogen Xanthomonas oryzae pv. oryzae (Xoo). Therefore, constructing structure-activity relationship (SAR) studies of DMEP is indispensable for new agrochemical discovery. In this study, we performed a structure-activity relationship (SAR) study of DMEP derivatives as potential XooFtsZ inhibitors through introducing the structure-based virtual screening (SBVS) approach and various biochemical methods. Notably, prepared compound B2, a 4'-acyloxy DMEP analog, had a 50% inhibitory concentration of 159.4 µM for inhibition of recombinant XooFtsZ GTPase, which was lower than that of the parent DMEP (278.0 µM). Compound B2 potently inhibited Xoo growth in vitro (minimum inhibitory concentration 153 mg L-1) and had 54.9% and 48.4% curative and protective control efficiencies against rice blight in vivo. Moreover, compound B2 also showed low toxicity for non-target organisms, including rice plant and mammalian cell. Given these interesting results, we provide a novel strategy to discover and optimize promising bactericidal compounds for the management of plant bacterial diseases.

GC-MS Profile of Hua-Feng-Dan and RNA-Seq Analysis of Induced Adaptive Responses in the Liver.

Background: Hua-Feng-Dan is a patent Chinese medicine for stroke recovery and various diseases. This study used GC-MS to profile its ingredients and RNA-Seq to analyze the induced adaptive response in the liver. Methods: Hua-Feng-Dan was subjected to steam distillation and solvent extraction, followed by GC-MS analysis. Mice were orally administered Hua-Feng-Dan and its "Guide drug" Yaomu for 7 days. Liver pathology was examined, and total RNA isolated for RNA-Seq, followed by bioinformatic analysis and quantitative real-time PCR (qPCR). Results: Forty-four volatile and fifty liposoluble components in Hua-Feng-Dan were profiled and analyzed by the NIST library and their concentrations quantified. The major components (>1%) in volatile (5) and liposoluble (10) were highlighted. Hua-Feng-Dan and Yaomu at hepatoprotective doses did not produce liver toxicity as evidenced by histopathology and serum enzyme activities. GO Enrichment revealed that Hua-Feng-Dan affected lipid homeostasis, protein folding, and cell adhesion. KEGG showed activated cholesterol metabolism, bile secretion, and PPAR signaling pathways. Differentially expressed genes (DEGs) were identified by DESeq2 with p < 0.05 compared to controls. Hua-Feng-Dan produced more DEGs than Yaomu. qPCR on selected genes largely verified RNA-Seq results. Ingenuity Pathways Analysis of the upstream regulator revealed activation of MAPK and adaptive responses by Hua-Feng-Dan, and Yaomu was less effective. Hua-Feng-Dan-induced DEGs were highly correlated with the Gene Expression Omnibus database of chemical-induced adaptive transcriptome changes in the liver. Conclusion: GC-MS primarily profiled volatile and liposoluble components in Hua-Feng-Dan. Hua-Feng-Dan at the hepatoprotective dose did not produce liver pathological changes but induced metabolic and signaling pathway activations. The effects of Hua-Feng-Dan on liver transcriptome changes point toward induced adaptive responses to program the liver to produce hepatoprotective effects.

Determination of 18 Trace Elements in 10 Batches of the Tibetan Medicine Qishiwei Zhenzhu Pills by Direct Inductively Coupled Plasma-Mass Spectrometry.

Qishiwei Zhenzhu pills (QSW) was first recorded in the Tibetan medicine classic Si Bu Yi Dian and has been used to treat "Baimai" disease, stroke, paralysis, hemiplegia, cerebral hemorrhage, and other diseases till today. This prescription contains more than 70 medicines including myrobalan, pearl, agate, opal, bezoar, coral, musk, gold, silver, and a mineral mixture Zuotai. As a result, QSW contains a large amount of mercury, copper, lead, and other trace elements. The aim of this study was to determine the 18 trace elements (lithium, beryllium, scandium, vanadium, chromium, manganese, cobalt, nickel, copper, arsenic, strontium, argentum, cadmium, cesium, barium, lead, aurum, and mercury) in 10 batches of QSW produced by 5 pharmaceutical companies (Ganlu Tibetan Medicine Co., Ltd. has 6 different batches) by direct inductively coupled plasma-mass spectrometry (ICP-MS). ICP-MS is a rapid, sensitive, accurate methodology allowing the determination of 18 elements simultaneously. The results showed that each element had an excellent linear relationship in the corresponding mass concentration range. The results showed that the rank order of the elements in QSW was copper > mercury > lead from high to low, with the mass fraction higher than 6000 µg/kg; the mass fractions of argentum, arsenic, manganese, aurum, strontium, barium, chromium, and nickel were in the range of 33-1034 µg/kg; and the mass fractions of vanadium, cobalt, lithium, beryllium, cadmium, scandium, and cesium were lower than 10 µg/kg. The reproducibility from the same manufacturer (Tibet Ganlu Tibetan Medicine Co., Ltd.) was relatively high; however, the element amounts among 5 manufacturers were different, which could affect the efficacy and toxicity of QSW. All in all, ICP-MS can be used as an effective tool for the analysis of trace elements in QSW and standard quality control needs to be enforced across different manufactures.

Tibetan Medicine Qishiwei Zhenzhu Pills Can Reduce Cerebral Ischemia-Reperfusion Injury by Regulating Gut Microbiota and Inhibiting Inflammation.

Cerebral ischemia is a series of harmful reactions, such as acute necrosis of tissue, inflammation, apoptosis, autophagy, and blood-brain barrier injury, due to the insufficient blood supply to the brain. Inflammatory response and gut microbiota imbalance are important concomitant factors of cerebral ischemia and may increase the severity of cerebral ischemia through the gut-brain axis. Qishiwei Zhenzhu pills (QSW) contain more than 70 kinds of medicinal materials, which have the effects of anti-cerebral infarction, anti-convulsion, anti-dementia, and so on. It is a treasure of Tibetan medicine commonly used in the treatment of cerebral ischemia in Tibetan areas. In this study, we gave rats QSW (66.68 mg/kg) once by gavage in advance and then immediately established the rat middle cerebral artery occlusion (MCAO) model. After 24 hours of treatment, the neuroprotection, intestinal pathology, and gut microbiota were examined. The results showed that QSW could significantly reduce the neurobehavioral abnormalities and cerebral infarction rate in MCAO rats. Furthermore, qPCR, western blot, and immunohistochemistry results showed that QSW could effectively inhibit IL-6, IL-1ß, and other inflammatory factors so as to effectively reduce the inflammatory response of MCAO rats. Furthermore, QSW could improve intestinal integrity and reduce intestinal injury. 16S rRNA sequencing showed that QSW could significantly improve the gut microbiota disorder of MCAO rats. Specifically, at the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the gut microbiota of rats with MCAO. At the genus level, it can adjust the abundance of Escherichia and Shigella. At the species level, it can adjust the abundance of Lactobacillus johnsonii and Lactobacillus reuteri. All in all, this study is the first to show that QSW can reduce the severity of cerebral ischemia-reperfusion injury by regulating gut microbiota and inhibiting the inflammatory response.

The Absorption, Distribution, and Excretion of 18 Elements of Tibetan Medicine Qishiwei Zhenzhu Pills in Rats with Cerebral Ischemia.

The aim of this study is to determine 18 elements in Tibetan medicine Qishiwei Zhenzhu pills (QSW) and their absorption, distribution, and excretion in rats with cerebral ischemia. Microwave digestion and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine 18 elements of QSW in simulated gastrointestinal (GI) juice. Rats were given QSW (66.68 mg/kg) followed by middle cerebral artery occlusion (MCAO). Sham rats received saline and were not subjected to MCAO. ICP-MS was applied to determine the content of 18 elements in hepatic venous blood, abdominal aortic blood, brain, liver, kidney, hair, urine, and feces 24 h after MCAO. In vitro results showed that the extraction rate of Mn, Cu, Sr, Pb, Au, and Hg of QSW in gastric juice (1 h) was higher than that in water, and the contents of Cu, Au, Sr, and As were higher in intestinal juice (4 h) than in water. In vivo results showed that the contents of elements in the blood were quite low, and QSW increased Ni, Cr, Sr, Co, and V in artery blood and decreased V in venous blood. Elements in the tissues were also low, and QSW increased brain Li but decreased Cr and Cd; QSW increased kidney Ag and Cs and liver Mn but decreased liver Ni. QSW increased urinary excretion of Li, Sr, Hg, Cs, and V; QSW increased Hg content in hair but decreased Ni. Stool is the main excretion pathway of the elements in QSW, with Ba, Mn, Sr, Cd, V, Cu, Cs, Li, Pb, Ag, Hg, Cr, As, and Co the highest. In summary, this study examined the distribution of 18 elements in QSW-treated MCAO rats. The accumulation of these elements in blood and tissues was extremely low, and the majority was excreted in feces within 24 h, highlighting the importance of the gut-microbiota-brain axis in QSW-mediated brain protection.

Synthesis of novel 18ß-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases.

BACKGROUND: The limited amount of agrochemicals targeting plant bacterial diseases has motivated us to study innovative antibacterial surrogates with fresh modes of action. Notably, fabrication of violent apoptosis inducers to control the reproduction of pathogenic bacteria should be a feasible way to control plant bacterial diseases. To achieve this aim, we constructed a series of novel 18ß-glycyrrhetinic piperazine amides based on the natural bioactive ingredient 18ß-glycyrrhetinic acid to evaluate the in vitro and in vivo antibacterial activity and induced apoptosis behaviors on tested pathogens. RESULTS: Screening results suggested that these designed compounds were extremely bioactive against two notorious pathogens, Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. This conclusion was highlighted by the biological effects of compounds A3 and B1 , affording the related EC50 values of 2.28 and 0.93 µg mL-1 . In vivo trials confirmed the prospective application for managing rice bacterial blight disease with control efficiency within 50.57-53.70% at 200 µg mL-1 . In particular, target compounds could induce the generation of excessive reactive oxygen species (ROS) in tested pathogens, subsequently leading to a strong apoptotic effect at a very low drug concentration (≤ 10 µg mL-1 ). This finding was consistent with the observed ROS-enhanced fluorescent images and morphological changes of pathogens from scanning electron microscopy patterns. CONCLUSION: Given these features, we anticipate that these novel piperazine-tailored 18ß-glycyrrhetinic hybrids can provide an perceptible insight for fighting bacterial infections by activation of the apoptosis mechanism. Novel 18ß-glycyrrhetinic piperazine amides were reported to have excellent antibacterial efficacy toward phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. A possible apoptosis mechanism was proposed from the remarkable apoptotic behaviors triggered by target compounds. © 2020 Society of Chemical Industry.