Accumulation mechanism of metabolite markers identified by machine learning between Qingyuan and Xiushui counties in Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua is a traditional Chinese medicinal plant acclaimed for its therapeutic potential in diabetes and various chronic diseases. Its rhizomes are the main functional parts rich in secondary metabolites, such as flavonoids and saponins. But their quality varies by region, posing challenges for industrial and medicinal application of P. cyrtonema. In this study, 482 metabolites were identified in P. cyrtonema rhizome from Qingyuan and Xiushui counties. Cluster analysis showed that samples between these two regions had distinct secondary metabolite profiles. Machine learning methods, specifically support vector machine-recursive feature elimination and random forest, were utilized to further identify metabolite markers including flavonoids, phenolic acids, and lignans. Comparative transcriptomics and weighted gene co-expression analysis were performed to uncover potential candidate genes including CHI, UGT1, and PcOMT10/11/12/13 associated with these compounds. Functional assays using tobacco transient expression system revealed that PcOMT10/11/12/13 indeed impacted metabolic fluxes of the phenylpropanoid pathway and phenylpropanoid-related metabolites such as chrysoeriol-6,8-di-C-glucoside, syringaresinol-4'-O-glucopyranosid, and 1-O-Sinapoyl-D-glucose. These findings identified metabolite markers between these two regions and provided valuable genetic insights for engineering the biosynthesis of these compounds.

Phillygenin Inhibits TGF-ß1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/ß-catenin Pathways.

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-ß1 (TGF-ß1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-ß1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-ß1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/ß-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. AIM OF THE STUDY: The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. METHODS: First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. RESULTS: A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. CONCLUSION: By combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.

A comprehensive review on pharmacological, toxicity, and pharmacokinetic properties of phillygenin: Current landscape and future perspectives.

Forsythiae Fructus is a traditional Chinese medicine frequently in clinics. It is extensive in the treatment of various inflammation-related diseases and is renowned as 'the holy medicine of sores'. Phillygenin (C21H24O6, PHI) is a component of lignan that has been extracted from Forsythiae Fructus and exhibits notable biological activity. Modern pharmacological studies have confirmed that PHI demonstrates significant activities in the treatment of various diseases, including inflammatory diseases, liver diseases, cancer, bacterial infection and virus infection. Therefore, this review comprehensively summarizes the pharmacological effects of PHI up to June 2023 by searching PubMed, Web of Science, Science Direct, CNKI, and SciFinder databases. According to the data, PHI shows remarkable anti-inflammatory, antioxidant, hepatoprotective, antitumour, antibacterial, antiviral, immunoregulatory, analgesic, antihypertensive and vasodilatory activities. More importantly, NF-κB, MAPK, PI3K/AKT, P2X7R/NLRP3, Nrf2-ARE, JAK/STAT, Ca2+-calcineurin-TFEB, TGF-ß/Smads, Notch1 and AMPK/ERK/NF-κB signaling pathways are considered as important molecular targets for PHI to exert these pharmacological activities. Studies of its toxicity and pharmacokinetic properties have shown that PHI has very low toxicity, incomplete absorption in vivo and low oral bioavailability. In addition, the physico-chemical properties, new formulations, derivatives and existing challenges and prospects of PHI are also reviewed and discussed in this paper, aiming to provide direction and rationale for the further development and clinical application of PHI.

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.

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking.

Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and p-NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis.

The protective effect of forsythiaside A on 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestatic liver injury in mice: Based on targeted metabolomics and molecular biology technology.

Cholestasis is a disorder of bile secretion and excretion caused by a variety of etiologies. At present, there is a lack of functional foods or drugs that can be used for intervention. Forsythiaside A (FTA) is a natural phytochemical component isolated from the medicinal plant Forsythia suspensa (Thunb.) Vahl, which has a significant hepatoprotective effect. In this study, we investigated whether FTA could alleviate liver injury induced by cholestasis. In vitro, FTA reversed the decrease in viability of human intrahepatic bile duct epithelial cells, the decrease in antioxidant enzymes (SOD1, CAT and GSH-Px), and cell apoptosis induced by lithocholic acid. In vivo, FTA protected mice from 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury, abnormal serum biochemical indexes, abnormal bile duct hyperplasia, and inflammatory infiltration. Furthermore, FTA treatment alleviated liver fibrosis by inhibiting collagen deposition and HSC activation. The metabonomic results showed that DDC-induced bile acid disorders in the liver and serum were reversed after FTA treatment, which may benefit from the activation of the FXR/BSEP axis. In addition, FTA treatment increased the levels of antioxidant enzymes in the serum and liver. Meanwhile, FTA treatment inhibited ROS and MDA levels and cleaved caspase 3 protein expression, thereby reducing DDC-induced hepatic oxidative stress and apoptosis. Further studies showed that the antioxidant effects of FTA were dependent on the activation of the BRG1/NRF2/HO-1 axis. In a word, FTA has a significant hepatoprotective effect on cholestatic liver injury, and can be further developed as a functional food or drug to prevent and treat cholestatic liver injury.

Celastrol as an emerging anticancer agent: Current status, challenges and therapeutic strategies.

Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicine Tripterygium wilfordii Hook F., which has multiple pharmacological activities. In particular, modern pharmacological studies have demonstrated that celastrol exhibits significant broad-spectrum anticancer activities in the treatment of a variety of cancers, including lung cancer, liver cancer, colorectal cancer, hematological malignancies, gastric cancer, prostate cancer, renal carcinoma, breast cancer, bone tumor, brain tumor, cervical cancer, and ovarian cancer. Therefore, by searching the databases of PubMed, Web of Science, ScienceDirect and CNKI, this review comprehensively summarizes the molecular mechanisms of the anticancer effects of celastrol. According to the data, the anticancer effects of celastrol can be mediated by inhibiting tumor cell proliferation, migration and invasion, inducing cell apoptosis, suppressing autophagy, hindering angiogenesis and inhibiting tumor metastasis. More importantly, PI3K/Akt/mTOR, Bcl-2/Bax-caspase 9/3, EGFR, ROS/JNK, NF-κB, STAT3, JNK/Nrf2/HO-1, VEGF, AR/miR-101, HSF1-LKB1-AMPKα-YAP, Wnt/ß-catenin and CIP2A/c-MYC signaling pathways are considered as important molecular targets for the anticancer effects of celastrol. Subsequently, studies of its toxicity and pharmacokinetic properties showed that celastrol has some adverse effects, low oral bioavailability and a narrow therapeutic window. In addition, the current challenges of celastrol and the corresponding therapeutic strategies are also discussed, thus providing a theoretical basis for the development and application of celastrol in the clinic.

Protective effects of dietary quercetin on cerebral ischemic injury: pharmacology, pharmacokinetics and bioavailability-enhancing nanoformulations.

Cerebral ischemia, as an ischemic stroke-like disease, has become a health problem of global concern. Studies have found that oxidative stress, inflammation, apoptosis, and impaired blood-brain barrier (BBB) and ion channel regulation are the basis for the development of cerebral ischemia pathology. Quercetin, a flavonoid compound, commonly found in the daily diet and in some Chinese herbal medicines, including vegetables, fruits, and tea, is one of the most prominent dietary antioxidants. Modern pharmacological studies have shown that quercetin can effectively protect against cerebral ischemic injury, and its mechanisms may involve antioxidant, anti-inflammatory, anti-apoptotic, BBB protection, ion channel regulation, cell excitatory glutamate toxicity alleviation and cognitive impairment recovery activities. However, the low bioavailability of quercetin and the presence of the BBB structure limit the therapeutic efficacy. There have been studies targeting the delivery of quercetin to the injury site through nanotechnology to enhance the therapeutic effect of quercetin. This review discusses and reviews the pharmacological activity, pharmacokinetic characteristics, and targeted delivery nanosystems of quercetin in protecting against cerebral ischemic injury, and provides information on various downstream signaling pathways regulated by quercetin, such as PI3k/Akt, MAPK, and Sirt1. We hope to provide a scientific basis for the development and application of quercetin in the field of cerebral ischemia.

CD44-Targeting Drug Delivery System of Exosomes Loading Forsythiaside A Combats Liver Fibrosis via Regulating NLRP3-Mediated Pyroptosis.

Liver fibrosis is a progressive pathological process induced by various stimuli and may progress to liver cirrhosis and cancer. Forsythiaside A (FA) is an active ingredient extracted from traditional Chinese medicine Forsythiae Fructus and has prominent hepatoprotective activities. However, the unsatisfactory pharmacokinetic properties restrict its clinical application. In this study, the nanocarrier of CD44-specific ligand Hyaluronic acid (HA)-modified milk-derived exosomes (mExo) encapsulated with FA (HA-mExo-FA) is developed. As a result, HA modification could deliver drug-loaded exosomes to the target cells and form a specific ligand-receptor interaction with CD44, thus improving the anti-liver fibrosis effect of FA. In vitro findings indicate that HA-mExo-FA could inhibit TGF-ß1-induced LX2 cell proliferation, reduce α-SMA and collagen gene and protein levels, and promote the apoptosis of activated LX2 cells. In vivo results demonstrate that HA-mExo-FA could improve liver morphology and function changes in zebrafish larvae. The anti-liver fibrosis mechanism of HA-mExo-FA may be attributed to the inhibition of NLRP3-mediated pyroptosis. In addition, the effect of HA-mExo-FA on TAA-induced increase in NLRP3 production is attenuated by NLRP3 inhibitor MCC950. Collectively, this study demonstrates the promising application of HA-mExo-FA in drug delivery with high specificity and provides a powerful and novel delivery platform for liver fibrosis therapy.

Phillygenin inhibited M1 macrophage polarization and reduced hepatic stellate cell activation by inhibiting macrophage exosomal miR-125b-5p.

Liver fibrosis (LF) is an important stage in chronic liver disease development, characterized by hepatic stellate cell (HSC) activation and excessive extracellular matrix deposition. Phillygenin (PHI), an active component in the traditional Chinese medicine Forsythiae Fructus with a significant anti-inflammatory effect, has been proved to inhibit HSC activation. Macrophages can polarize to pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype, participating in LF development. Currently, Forsythiae Fructus and its many components have been proved to inhibit the inflammatory activation of macrophages. However, there is no direct evidence that PHI can regulate macrophage polarization, and the relationship between macrophage polarization and the anti-LF effect of PHI has not been studied. In this study, we found that PHI inhibited the co-expression of CD80 and CD86, and inhibited the mRNA expression and protein secretion of related inflammatory cytokines in RAW264.7 cells. For mechanism, PHI was found to inhibit the JAK1/JAK2-STAT1 and Notch1 signaling pathways. Subsequently, mHSCs were co-cultured with the conditioned media or exosomes from macrophages with different treatments. It was found that the conditioned media and exosomes from PHI-treated macrophages inhibited the expression of MMP2, TIMP1, TGF-ß, α-SMA, COL1 and NF-κB in mHSCs. Moreover, through bioinformatic analysis and cell transfection, we confirmed that PHI reduced HSC activation by inhibiting the overexpression of miR-125b-5p in M1 macrophage-derived exosomes and restoring Stard13 expression in mHSCs. On the whole, PHI could inhibit M1 macrophage polarization by suppressing the JAK1/JAK2-STAT1 and Notch1 signaling pathways, and reduce HSC activation by inhibiting macrophage exosomal miR-125b-5p targeting Stard13. DATA AVAILABILITY: The raw data supporting the conclusions of this study are available in the article/Supplementary figures, and can be obtained from the first or corresponding author.

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 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.

Identification of Hair Growth Promoting Components in the Kernels of Prunus mira Koehne and Their Mechanism of Action.

The application of the seed oil of Prunus mira Koehne (Tibetan name ཁམབུ།), a plant belonging to the Rosaceae family, for the treatment of alopecia has been recorded in Jingzhu Materia Medica (ཤེལ་གོང་ཤེལ་ཕྲེང་།) (the classic of Tibetan medicine) and Dictionary of Chinese Ethnic Medicine. This study aims to reveal the effective components and mechanism of hair growth promotion in the kernel of Prunus mira Koehne. Network pharmacology was used to predict the mechanism of action and effective components in the treatment of the kernel of Prunus mira Koehne. The contents of amygdalin in 12 batches of the kernel of Prunus mira Koehne were determined by HPLC. An animal model of the depilation of KM mice induced by sodium sulfide was created, and five effective components that promoted hair growth were initially screened. In the study of the effectiveness and mechanism of action, KM and C57BL/6 mice are selected as experimental objects, three screening tests for active components of the kernel of P. mira are performed, and three effective components are screened out from the eight components. HE staining was used to detect the number of hair follicles and the thickness of the dermis. RT-PCR and immunohistochemistry were used to evaluate the influence of the expression of indicators in the Wnt/ß-catenin signaling pathway in skin, including ß-catenin, GSK-3ß, and mRNA and protein expression levels of Cyclin D 1 and LEF 1. The network pharmacology study showed 12 signaling pathways involving 25 targets in the treatment of alopecia by the kernel of Prunus mira Koehne. vitamin E (3.125 mg/cm2/d), ß-sitosterol (0.061 mg/cm2/d), and linoleic acid (0.156 mg/cm2/d) in the kernel of Prunus mira Koehne can promote hair growth in mice, and the mechanism of action may be related to the Wnt/ß-catenin pathway.

Progress in ICP-MS Analysis of Minerals and Heavy Metals in Traditional Medicine.

Aim: This study systematically reviewed the application of ICP-MS and its combined technology in the determination of mineral and heavy metal elements in medicinal materials derived from plants, animals, minerals and their preparations (Chinese patent medicine), and biological products. It provides a reference for improving the quality standard of traditional medicine and exploring the effective components, toxic components, and action mechanism of traditional medicine. Materials and Methods: A total of 234 articles related to the determination of mineral and heavy metal elements in medicinal materials derived from plants, animals, and minerals and their preparations (Chinese patent medicine) were collected from PubMed, CNKI, Web of Science, VIP, and other databases. They were classified and sorted by the inductively coupled plasma-mass-spectrometry (ICP-MS) method. Results: Of the 234 articles, 154 were about medicinal materials derived from plants, 15 about medicinal materials derived from animals, 9 about medicinal materials derived from minerals, 46 about Chinese patent medicine, 10 about combined technology application, and 3 about drugs being tested after entering the body. From the 154 articles on medicinal materials derived from plants, 76 elements, including Cu, Cd, Pb, As, Cr, Mn, and Hg, were determined, of which the determination of Cu was the most, with 129 articles. Medicinal materials derived from the roots, stems, leaves, flowers, and fruits and seeds of plants accounted for 25.97%, 18.18%, 7.14%, 7.79%, and 14.94%, respectively. Moreover, medicinal materials derived from the whole plants accounted for 14.94%, and other medicinal materials derived from plants and soil accounted for 11.04%. A total of 137 of the tested medicinal materials were from traditional Chinese medicine, accounting for 88.96%, 12 were from Arabic medicine (including Unani), accounting for 7.79%, 2 were from Tibetan medicine of China, and 1 was from Mongolian medicine of China, 1 was from Miao medicine of China, and 1 was from Zhuang medicine of China. In the 15 articles on medicinal materials derived from animals, 49 elements such as Cu, As, Cd, Hg, Se, Pb, and Mn were determined, of which Cu was the most. All the tested medicinal materials belong to traditional Chinese medicine. From the nine articles on medicinal materials derived from minerals, 70 elements such as Fe, Cu, Zn, Al, As, Se, and Na were determined, of which Fe, Cu, and Zn were the most. The tested medicinal materials all belong to traditional Chinese medicine. From the 46 articles on Chinese patent medicine, 62 elements such as Cu, As, Pb, Cd, Hg, Ni, and Cr were determined, of which Cu was the most. Regarding the tested Chinese patent medicine, 38 articles belong to traditional Chinese medicine, 6 to Tibetan medicine, and 2 to Mongolian medicine of China. Three articles determine the content of metal elements in biological samples such as animal hepatic venous blood, abdominal aortic blood, brain, liver, kidney, urine, and feces, and one article determines the content of metal elements in human lung and serum. From the 10 articles combined with liquid chromatography and gas chromatography, 16 elements such as MMA, DMA, AsIII, AsV, AsB, AsC, and AsI3 were determined, of which MMA and DMA were the most. It can realize elemental morphology and isotope analysis. The tested medicinal materials and Chinese patent medicine belong to traditional Chinese medicine. Conclusion: ICP-MS was applied the most in traditional Chinese medicine, followed by Arabic medicine. ICP-MS was used to determine more medicinal materials derived from plants, and Cu was determined the most. The characteristic inorganic element spectrum of medicinal materials can also be established. ICP-MS and its combined technology are widely used in Chinese patent medicine, but the test of biological samples is the least. The information provided in this article can provide a reference for improving the quality standard of traditional medicines and exploring the active ingredients and toxic ingredients and their mechanism of action.

Hepatoprotective effect of phillygenin on carbon tetrachloride-induced liver fibrosis and its effects on short chain fatty acid and bile acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythiae fructus, the dried fruit of Oleaceae plant Forsythia suspensa (Thunb.) Vahl, is a traditional Chinese medicine widely used in clinical practice and has a variety of pharmacological activities, such as anti-inflammation, antioxidation, and hepatoprotection. AIM OF THE STUDY: Phillygenin (PHI), an important fingerprint lignan component of Forsythiae fructus, has prominent hepatoprotective, anti-inflammatory and antioxidant effects. Previously, it was shown that PHI could exert anti-fibrotic effects by modulating inflammation and gut microbiota. Therefore, given the important roles of SCFAs and BAs in the development of liver fibrosis, as well as their close links with gut microbiota, we aimed to determine the protective effects of PHI on carbon tetrachloride (CCl4)-induced liver fibrosis and its effects on the metabolism of SCFAs and BAs based on metabolomics. MATERIALS AND METHODS: In C57BL/6J mice, liver fibrosis model was established by intraperitoneal injection of olive oil containing 10% CCl4 for 4 weeks. Firstly, the mouse liver tissues were subjected to histological analysis and biochemical index assay to evaluate the protective effect of PHI on CCl4-induced liver fibrosis. Subsequently, the effects of PHI on the metabolism of SCFAs and BAs in CCl4-induced liver fibrosis mice were determined using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) for metabolomics analysis. Finally, the levels of the closely related proteins and genes were detected by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) to explore the underlying mechanisms of the protective effect of PHI on CCl4-induced liver fibrosis. RESULTS: The histological analysis and the determination of relevant biochemical indexes of liver tissues showed that PHI could attenuate CCl4-induced liver fibrosis. The metabolomic analysis on SCFAs showed that PHI could promote SCFA production in the gut of mice with CCl4-induced liver fibrosis, especially acetic acid, propionic acid and butyric acid. It has been reported that the increased production of SCFAs was possibly beneficial to health. The metabolomic analysis on BAs found that PHI could restore the disturbance of BA metabolism in mice with CCl4-induced liver fibrosis. The immunohistochemistry and RT-qPCR results confirmed that PHI could ameliorate intestinal epithelial barrier disruption, and reverse the expression of BA metabolism-related genes in mice with CCl4-induced liver fibrosis. CONCLUSIONS: Promoting the production of SCFAs in the gut and restoring the disturbance of BA metabolism may be the potential mechanisms by which PHI alleviated CCl4-induced liver fibrosis.

Forsythiaside A alleviated carbon tetrachloride-induced liver fibrosis by modulating gut microbiota composition to increase short-chain fatty acids and restoring bile acids metabolism disorder.

Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to investigate the protective effect of FTA on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 mL/kg CCl4 three times a week for 4 weeks. FTA attenuated CCl4-induced liver fibrosis in mice, which was proved by the results of Masson and Sirius red staining, liver hydroxyproline, hyaluronic acid, laminin, type III procollagen, and type IV collagen assays. FTA inhibited hepatic stellate cell activation, and reduced hepatic inflammation and oxidative stress in mice treated with CCl4. What's more, FTA ameliorated CCl4-induced gut dysbiosis, maintained intestinal barrier function, increased the production of short-chain fatty acids (SCFAs), and improved endotoxemia, as manifested by decreased serum lipopolysaccharide levels and increased expression of ileal tight junction proteins. Besides, FTA can modulate the genes related to bile acid metabolism to alter the distribution of fecal BAs in fibrotic mice. In a word, FTA can improve liver fibrosis by inhibiting inflammation and oxidative stress, regulating gut microbiota and BA metabolism, and increasing the content of SCFAs. The results of this study provided an important reference for the study on the mechanisms by which natural products prevent liver fibrosis.

A review: Pharmacology and pharmacokinetics of Schisandrin A.

Schisandrin A (SA) is a bioactive lignan isolated from the traditional Chinese medicine Fructus schisandrae chinensis. In recent years, it has attracted extensive attention because of its multiple pharmacological activities. This review is the first to provide an overview of SA-related pharmacological effects and pharmacokinetic characteristics. The results showed that SA had many pharmacological effects, such as antiinflammation, anticancer, hepatoprotection, antioxidation, neuroprotection, antidiabetes mellitus, and musculoskeletal protection. Among them, NF-κB, Nrf2, MAPK, NLRP3, PI3K/AKT, Wnt, miRNA, P-gp, CYP450, PXR, and other signal transduction pathways are involved. Pharmacokinetic studies showed that SA had good pharmacokinetic characteristics, but these were affected by other factors, such as drugs or hepatic fibrosis. Thus, SA has a variety of pharmacological effects and good pharmacokinetic characteristics, which is worthy of further research and development in the future.

Traditional medicine in China for ischemic stroke: bioactive components, pharmacology, and mechanisms.

Ischemic stroke is an acute cerebrovascular disease and the third most common cause of death after ischemic heart disease. Increasing attention is being paid to finding effective treatments through traditional medicine. Thus, studying the traditional medicine for the treatment of ischemic stroke is of great importance. Traditional medicine in China includes traditional Chinese medicine (TCM) and other ethnic medicines, which is rich in variety and resources. This review first introduces the treatment mechanisms associated with ischemic stroke, such as antioxidant nitrification, antiexcitotoxic, antiapoptotic, anti-inflammatory, antiplatelet and anticoagulation mechanisms. Then, we calculated the frequency of prescription use for ischemic stroke and summarized the treatments for ischemic stroke by investigating 13 drug monographs and standards. We found 192 prescriptions from the traditional medical system for ischemic stroke, including Angong Niuhuang pill, Qishiwei Zhenzhu Pills, Ginkgo biloba leaf, and other traditional Chinese patent medicines and national medicines. There were 398 kinds of traditional medicine, including 301 kinds of plant-based medicines, 54 kinds of animal-based medicines, 28 kinds of mineral-based medicines, and 15 kinds of other medicines. We introduced the names, families, medicinal components, traditional uses, phytochemical information, and pharmacological activities of the commonly used Chinese patent medicines and TCMs. In addition, some chemicals were introduced. These medicines may be potential candidates for the treatment of ischemic stroke. This work provides a reference for the research and clinical use of new drugs for ischemic stroke.

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.