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.

Genome-wide identification of CBL gene family in Salvia miltiorrhiza and the characterization of SmCBL3 under salt stress.

In plants, CBL mediated calcium signaling is widely involved in the response to plant stresses of adversity. However, to date, no comprehensive studies have been conducted on CBL family members in Salvia miltiorrhiza. Herein, we identified 8 SmCBLs in S. miltiorrhiza, and phylogenetic analysis classified SmCBLs into four groups. Analysis of cis-acting elements revealed that SmCBLs mostly have light-responsive and hormone-responsive elements. Tissue expression analysis indicated that almost all of SmCBLs were expressed in roots than in leaves and flowers. SmCBL3 responded to Abscisic Acid (ABA), polyethylene glycol (PEG), and NaCl treatments. Transgenic Arabidopsis thaliana that overexpressed SmCBL3 had higher germination rates and longer roots than the wild type (WT) when exposed to salt stress. Additionally, the transgenic lines exhibited higher levels of chlorophyll, proline, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activity and SOS1, NHX1 and P5CS1 expression than WT, and lower levels of malondialdehyde (MDA). Furthermore, SmCBL3 interacts with SmCIPK9. In conclusion, we analyzed the protein physicochemical properties, evolutionary relationships, gene structures, and expression profiles of the SmCBL gene families in S. miltiorrhiza. Overexpression of SmCBL3 improves the salt tolerance of transgenic Arabidopsis. This study demonstrated that SmCBL3 is a positive regulator of plant salt tolerance, so the use of overexpressed SmCBL3 may serve as a potential strategy to enhance plant salt tolerance.

[Chemical constituents from whole herb of Hedyotis scandens].

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 µg·mL~(-1), respectively.

Commiphora mukul (Hook. ex Stocks) Engl.: Historical records, application rules, phytochemistry, pharmacology, clinical research, and adverse reaction.

ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora mukul (Hook. ex Stocks) Engl. (also known as Guggulu) is one of the oldest and most prominent herb used in Ayurvedic medicine. Commiphora mukul plants have traditionally been used to treat inflammation, diabetes, rheumatism, arthritis, obesity, and hyperlipidemia. It has long been used in China, India, Greece, and other countries. Commiphora mukul is an over-the-counter dietary supplement in the United States and Western countries. Commiphora mukul has excellent medicinal and commercial value and deserves further investigation. AIM OF THE STUDY: This paper systematically reviews the historical records, application rules, phytochemistry, pharmacokinetics, pharmacology, clinical research, and adverse reactions of C. mukul and provides a reference for its comprehensive application in basic research, new drug development, and clinical treatment. MATERIALS AND METHODS: Literature were collected from databases such as PubMed, CNKI, Web of Science, TBRC, and other sources such as ancient books on traditional medicine, classic books on herbal medicine, and modern monographs. In this study, the application history and modern pharmacological research on C. mukul in the medicine of all ethnic groups were comprehensively and systematically reviewed. RESULTS: According to the vast literature, the varieties, morphological characteristics, distribution, and description of C. mukul used in Unani medicine, Ayurveda, traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uygur medicine are highly consistent. Commiphora mukul is mainly used to treat rheumatoid arthritis, heart disease, obesity, hemorrhoids, urinary system diseases, skin diseases, inflammation, diabetes, hyperlipidemia, tumors, and other diseases. The core medicinal material combination in different ethnic medical preparations was C. mukul-Terminalia chebula Retz. (101 times), C. mukul-Moschus (55 times), C. mukul-Aucklandia lappa (Decne.) Decne. (52 times), and C. mukul-Acorus calamus L (27 times). Phytochemical studies confirmed that 150 components with different structures had been isolated and identified. Z-and E-guggulsterone are the main isomers in C. mukul. C. mukul has anti-cancer, anti-inflammatory, antioxidant, hypolipidemic, bone resorption, nervous system protection, myocardial protection, antibacterial, and other pharmacological properties. Clinical studies have only identified the role of C. mukul in treating hemorrhoids and lowering blood lipids. CONCLUSIONS: As an essential traditional medicine, C. mukul is widely used in the national traditional medicine system, and rich in chemical constituents and exhibit pharmacological activities. This study found that current research on C. mukul mainly focuses on its chemical composition and pharmacological properties. However, scientific research on the quality control of medicinal materials, identification of original plants, pharmacokinetics, and toxicology are relatively weak, and research in this area needs to be strengthened.

Mass Spectrometry Imaging as a New Method: To Reveal the Pathogenesis and the Mechanism of Traditional Medicine in Cerebral Ischemia.

Mass spectrometry imaging (MSI) can describe the spatial distribution of molecules in various complex biological samples, such as metabolites, lipids, peptides and proteins in a comprehensive way, and can provide highly relevant supplementary information when combined with other molecular imaging techniques and chromatography techniques, so it has been used more and more widely in biomedical research. The application of mass spectrometry imaging in neuroscience is developing. It is very advantageous and necessary to use MSI to study various pathophysiological processes involved in brain injury and functional recovery during cerebral ischemia. Therefore, this paper introduces the techniques of mass spectrometry, including the principle of mass spectrometry, the acquisition and preparation of imaging samples, the commonly used ionization techniques, and the optimization of the current applied methodology. Furthermore, the research on the mechanism of cerebral ischemia by mass spectrometry was reviewed, such as phosphatidylcholine involved, dopamine, spatial distribution and level changes of physiological substances such as ATP in the Krebs cycle; The characteristics of mass spectrometry imaging as one of the methods of metabolomics in screening biomarkers related to cerebral ischemia were analyzed the advantages of MSI in revealing drug distribution and the mechanism of traditional drugs were summarized, and the existing problems of MSI were also analyzed and relevant suggestions were put forward.

Thiol-functionalized nano-silica for in-situ remediation of Pb, Cd, Cu contaminated soils and improving soil environment.

Heavy metal contamination has been threatening the health of human beings. To decrease the bio-toxicity of heavy metals, a thiol-functionalized nano-silica (SiO2-SH) was adopted to remediate the soil contaminated by lead (Pb), cadmium (Cd) and copper (Cu). The remediation effect of SiO2-SH on contaminated soils was investigated by the uptake of the heavy metals into lettuce and pakchoi in pot experiment. The bio-toxicity of the SiO2-SH was evaluated, and its immobilization mechanisms were proposed by the fraction distribution of Cd, Pb and Cu. It was found that the SiO2-SH can significantly reduce the uptake of Cd, Pb, Cu into pakchoi by 92.02%, 68.03%, 76.34% and into lettuce by 89.81%, 43.41%, 5.76%, respectively. The chemical species analyses of Cd, Pb, Cu indicate SiO2-SH can transform the heavy metal in acid soluble states into reducible fraction and oxidizable fraction, thereby inhibiting the extraction of heavy metals into soil solution. The concentrations of microbial biomass carbon, organic matter, and cation exchange capacity of the soil increased while the soil bulk density decreased after remediation. Those changes demonstrate that SiO2-SH not only has no bio-toxic impact on the soil environment but also improves the soil environment, which proves the prepared SiO2-SH is environmental-friendly. The SiO2-SH could be a promising amendment for heavy metal contaminated soils.