Repair-driven DNA tetrahedral nanomachine combined with DNAzyme for 8-oxo guanine DNA glycosylase activity assay, drug screening and intracellular imaging.

8-oxo guanine DNA glycosylase (8-oxoG DNA glycosylase), a crucial DNA repair enzyme, is essential for maintaining genome integrity and preventing diseases caused by DNA oxidative damage. Imaging 8-oxoG DNA glycosylase in living cells requires a dependable technique. In this study, we designed a DNAzyme-modified DNA tetrahedral nanomachine (DTDN) powered by 8-oxoG restoration. Incorporating a molecular beacon probe (MB), the constructed platform was used for amplified in situ monitoring of 8-oxoG DNA glycosylase. Under normal conditions, duplexing with a complementary strand modified with two 8-oxoG sites inhibited the activity of DNAzyme. The restoration of DNAzyme activity by the repair of intracellular 8-oxoG DNA glycosylase on 8-oxoG bases can initiate a signal amplification reaction. This detection system can detect 8-oxoG DNA glycosylase activity linearly between 0 and 20 U mL-1, with a detection limit as low as 0.52 U mL-1. Using this method, we were able to screen 14 natural compounds and identify 6 of them as 8-oxoG DNA glycosylase inhibitors. In addition, a novel approach was utilized to assess the activity of 8-oxoG DNA glycosylase in living cells. In conclusion, this method provides a universal tool for monitoring the activity of 8-oxoG DNA glycosylase in vitro and in living cells, which holds great promise for elucidating the enzyme's functionality and facilitating drug screening endeavors.

Dibenzocyclooctadiene lignans from the family Schisandraceae: A review of phytochemistry, structure-activity relationship, and hepatoprotective effects.

Liver injury is a common pathological process characterized by massive degeneration and abnormal death of liver cells. With increase in dead cells and necrosis, liver injury eventually leads to nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and even hepatocellular carcinoma (HCC). Consequently, it is necessary to treat liver injury and to prevent its progression. The drug Bicylol is widely employed in China to treat chronic hepatitis B virus (HBV) and has therapeutic potential for liver injury. It is the derivative of dibenzocyclooctadiene lignans extracted from Schisandra chinensis (SC). The Schisandraceae family is a rich source of dibenzocyclooctadiene lignans, which possesses potential liver protective activity. This study aimed to comprehensively summarize the phytochemistry, structure-activity relationship and molecular mechanisms underlying the liver protective activities of dibenzocyclooctadiene lignans from the Schisandraceae family. Here, we had discussed the analysis of absorption or permeation properties of 358 compounds based on Lipinski's rule of five. So far, 358 dibenzocyclooctadiene lignans have been reported, with 37 of them exhibited hepatoprotective effects. The molecular mechanism of the active compounds mainly involves antioxidative stress, anti-inflammation and autophagy through Kelch-like ECH-associating protein 1/nuclear factor erythroid 2 related factor 2/antioxidant response element (Keap1/Nrf2/ARE), nuclear factor kappa B (NF-кB), and transforming growth factor ß (TGF-ß)/Smad 2/3 signaling pathways. This review is expected to provide scientific ideas for future research related to developing and utilizing the dibenzocyclooctadiene lignans from Schisandraceae family.

Understanding the key functions of Myosins in viral infection.

Myosins, a class of actin-based motor proteins existing in almost any organism, are originally considered only involved in driving muscle contraction, reshaping actin cytoskeleton, and anchoring or transporting cargoes, including protein complexes, organelles, vesicles. However, accumulating evidence reveals that myosins also play vital roles in viral infection, depending on viral species and infection stages. This review systemically summarizes the described various myosins, the performed functions, and the involved mechanisms or molecular pathways during viral infection. Meanwhile, the existing issues are also discussed. Additionally, the important technologies or agents, including siRNA, gene editing, and myosin inhibitors, would facilitate dissecting the actions and mechanisms for described and undescribed myosins, which could be adopted to prevent or control viral infection are also characterized.

A Review of Polygonatum Mill. Genus: Its Taxonomy, Chemical Constituents, and Pharmacological Effect Due to Processing Changes.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Polygonatum Tourn, ex Mill. contains numerous chemical components, such as steroidal saponins, polysaccharides, flavonoids, alkaloids, and others, it possesses diverse pharmacological activities, such as anti-aging, anti-tumor, immunological regulation, as well as blood glucose management and fat reducing properties. AIM OF THE REVIEW: This study reviews the current state of research on the systematic categorization, chemical composition, pharmacological effects, and processing changes of the plants belonging to the genus Polygonatum, to provide a theoretical foundation for their scientific development and rational application. MATERIALS AND METHODS: The information was obtained by searching the scientific literature published between 1977 and 2022 on online databases (including PubMed, CNKI, SciFinder, and Web of Science) and other sources (such as the Chinese Pharmacopoeia 2020 edition, and Chinese herbal books). RESULTS: The genus Polygonatum contains 79 species, and 233 bioactive chemical compounds were identified in them. The abundance of pharmacological activities, such as antioxidant activities, anti-fatigue activities, anti-inflammatory activities, etc., were revealed for the representatives of this genus. In addition, there are numerous processing methods, and many chemical constituents and pharmacological activities change after the unappropriated processing. CONCLUSIONS: This review summarizes the taxonomy classification, chemical composition, pharmacological effects, and processing of the plants belonging to the genus Polygonatum, providing references and research tendencies for plant-based drug development and further clinical applications.

Anti-gastric cancer activity and mechanism of natural compound "Heilaohulignan C" isolated from Kadsura coccinea.

In this research, we analyzed the antitumor activity of one new compound Heilaohulignan C (B-6) on the human gastric carcinoma cells. MTT, cell migration, Calcein AM/Propidium Iodide (PI), and flow cytometry in BGC-823 cell line (gastric tumor). Western blot was utilized to distinguish the protein level. Xenografts nude mice were used for in vivo anticancer analysis. H&E staining and laboratory investigation was accomplished for toxicity study. MTT test demonstrated the cytotoxicity of BGC-823 cells, Calcein AM/Propidium Iodide (PI) examine indicated increment dead cells proportion with a high dose of B-6, Flow cytometry (FACS) measure showed that B-6 influenced gastric cancer cells by initiating apoptosis. Western blot analysis confirmed that (B-6) decrease the level of Bcl-2 and increase the level of p53, Bax, and cleaved Caspase-3, this confirms that the B-6 doing the apoptosis through caspase and cytochrome C apoptotic pathways. Also, B-6 particularly decline the tumor volume and tumor size in the xenograft mice. H&E staining additionally supports that B-6 does not have any toxic impact on the normal tissues. This research supports that B-6 have pharmacological activity against gastric cancer, by p53 and mitochondrial dependent apoptotic pathway, and have no toxicity on normal tissues.

Tumor Progression Locus 2 in Hepatocytes Potentiates Both Liver and Systemic Metabolic Disorders in Mice.

Tumor progression locus 2 (TPL2), a serine/threonine kinase, has been regarded as a potentially interesting target for the treatment of various diseases with an inflammatory component. However, the function of TPL2 in regulating hepatocyte metabolism and liver inflammation during the progression of nonalcoholic fatty liver disease (NAFLD) is poorly understood. Here, we report that TPL2 protein expression was significantly increased in fatty liver from diverse species, including humans, monkeys, and mice. Further investigations revealed that compared to wild-type (WT) littermates, hepatocyte-specific TPL2 knockout (HKO) mice exhibited improved lipid and glucose imbalance, reserved insulin sensitivity, and alleviated inflammation in response to high-fat diet (HFD) feeding. Overexpression of TPL2 in hepatocytes led to the opposite phenotype. Regarding the mechanism, we found that mitogen-activated protein kinase kinase 7 (MKK7) was the specific substrate of TPL2 for c-Jun N-terminal kinase (JNK) activation. TPL2-MKK7-JNK signaling in hepatocytes represents a promising drugable target for treating NAFLD and associated metabolic disorders. Conclusion: In hepatocytes, TPL2 acts as a key mediator that promotes both liver and systemic metabolic disturbances by specifically increasing MKK7-JNK activation.

Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis.

Seven cyclic depsipeptides were isolated from Hapsidospora irregularis and structurally characterized as the calcium channel blocker leualacin and six new analogues based on the NMR and HRESIMS data. These new compounds were named leualacins B-G. The absolute configurations of the amino acids and 2-hydroxyisocaproic acids were determined by recording the optical rotation values. Biological studies showed that calcium influx elicited by leualacin F in primary human lobar bronchial epithelial cells involves the TRPA1 channel. Through genome sequencing and targeted gene disruption, a noniterative nonribosomal peptide synthetase was found to be involved in the biosynthesis of leualacin. A comparison of the structures of leualacin and its analogues indicated that the A2 and A4 domains of the leualacin synthetase are substrate specific, while A1, A3, and A5 can accept alternative precursors to yield new molecules.

Quantitative and qualitative determination of LiuweiDihuang preparations by ultra high performance liquid chromatography in dual-wavelength fingerprinting mode and random forest.

The classical traditional Chinese formulation LiuweiDihuang, shown to have clinical efficacy for "nourishing kidney-yin" in traditional Chinese medicine, has been used for thousands of years in China. Little attention, however, has been paid to quality control methods for this formulation. Hence, a rapid and sensitive analytical technique is urgently needed for the evaluation of LiuweiDihuang preparations to assess its quality and pharmacological functionality. In this study, an ultra high performance liquid chromatography dual-wavelength method was developed to simultaneously determine 11 constituents in LiuweiDihuang preparations. This robust approach provided a fast and comprehensive quantitative determination of the major bioactive markers within LiuweiDihuang preparations. To distinguish four dosage forms of LiuweiDihuang preparations, a random forest technique was applied on the spectrometric fingerprint data obtained. This combination approach of chromatographic techniques and data analyses might serve as a rapid and efficient tool to ensure the quality of LiuweiDihuang preparations and other Chinese medicinal formulations and can support quality control and scientific research into the pharmacological potential for these formulations.

Exosomes as Powerful Biomarkers in Cancer: Recent Advances in Isolation and Detection Techniques.

Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials' signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures.

Dual-driven AND molecular logic gates for label-free and sensitive ratiometric fluorescence sensing and inhibitors screening.

Due to the complexity of regulatory networks of disease-related biomarkers, developing simple, sensitive, and accurate methods has remained challenging for precise diagnosis. Herein, an "AND" logic gates DNA molecular machine (LGDM) was constructed, which was powered by the catalytic hairpin assembly (CHA). It was coupled with dual-emission CdTe quantum dots (QDs)-based cation exchange reaction (CER) for label-free, sensitive, and ratiometric fluorescence detection of APE1 and miRNA biomarkers. Benefiting from synergistic signal amplification strategies and a ratiometric fluorometric output mode, this LGDM enables accurate logic computing with robust and significant output signals from weak inputs. It offers improved sensitivity and selectivity even in cell extracts. Using dual-emission spectra CdTe QDs, with a ratiometric signal output mode, ensured good stability and effectively prevented false-positive signals from intrinsic biological interferences compared to the approach relying on a single signal output mode, which enabled the LGDM to achieve rapid, efficient, and accurate natural drug screening against APE1 inhibitors in vitro and cells. The developed method provides impetus to streamline research related to miRNA and APE1, offering significant promise for widespread application in drug development and clinical analysis.

Pushing Forward the DNA Walkers in Connection with Tumor-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018-2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future.

Differential analysis of phytochemistry and antioxidant activity in five citrus by-products based on chromatography, mass spectrometry, and spectrum-effect relationships.

The unripe fruit or peel of Citrus aurantium L., Citrus sinensis Osbeck, and Citrus reticulata Blanco are often disregarded due to perceptions of their marginal value. The present study was undertaken to explore the differences in phytochemical composition and bioactive properties of five citrus by-products in China and demonstrate their potential value. 214 compounds were systematically identified using LC-Orbitrap-MS analysis. Among them, narirutin, naringin, hesperidin, and neohesperidin were established as essential compounds for the discrimination and authentication of the five by-products via a combination of LC-MS, HPLC, and TLC techniques. Variations in the antioxidant activity of the by-products were observed, which correlated with their maturity and were attributable to differences in their active ingredients. Moreover, spectrum-effect relationship analysis revealed that the four previously identified differential markers, along with nobiletin and tangeretin, significantly contributed to the differences in antioxidant activity. The results highlight the potential for citrus by-product enhancement and utilization.

Biomimetic Hybrid Membrane-Coated Xuetongsu Assisted with Laser Irradiation for Efficient Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease underlying a cascade of chronic inflammatory processes. Over the past decades, the response rate of effective RA treatments has remained scarce despite numerous advancements in the current therapeutic interventions, owing largely to the associated off-target adverse events and poor accumulation in the inflamed joints. Recently, there is a high interest in the development of targeted drug delivery system by using nanotechnology, as it can provide a handle to improve the therapy efficacy of RA. Here, multifunctional HA@RFM@PB@SE nanoparticles (HRPS NPs) are developed by loading schisanlactone E (SE, also called with xuetongsu), an anti-RA compound isolated from Tujia ethnomedicine xuetong, into Prussian blue nanoparticles (PB NPs) and further camouflage of RBC-RAFLS hybrid membrane with HA modification onto PB@SE NPs (PS NPs). We demonstrated that the modification of RFM makes PB NPs ideal decoys for targeting inflammatory mediators of arthritis due to the homing effects of the parental cells. Moreover, the encapsulation of RFM on the PB@SE NPs extended the blood circulation time and improved its targeting ability, which accordingly achieved optimal accumulation of SE in arthritic rat paws. In vitro and in vivo assay demonstrated the outstanding performance of HRPS NPs for synergistic chemo-/photothermal therapy of RA without side effects to healthy tissues. Molecular mechanism exploration indicated that the ultrastrong inhibition of synovial hyperplasia and bone destruction was partly via suppressing NF-κB signaling pathway and the expression of matrix metalloproteinases. In summary, the nanodrug delivery system showed controllable release behavior, targeted accumulation at arthritic sites and systemic regulation of immunity, hence improved therapeutic efficacy and clinical outcomes of the disease without attenuating safety.

Pseudorabies in pig industry of China: Epidemiology in pigs and practitioner awareness.

Pseudorabies virus (PRV) is widely prevalent in China, which can transmit from pigs to other mammals. Moreover, a PRV variant isolated from an acute human encephalitis case was documented recently. It is imperative to investigate PRV epidemiology in pigs, the knowledge regarding pseudorabies (PR) and self-protection behaviors upon working among relevant practitioners including pig farmers, pig cutters, and pork salesman. In the present study, 18,812 pig serum samples and 1,634 tissue samples were collected from Hunan Province during the period of 2020 to 2021 for detecting the presence of PRV gE-special antibody and nucleic acids, respectively. Meanwhile, we conducted a questionnaire survey about PR among these practitioners in China. The results showed that nearly 9% (1,840/20,192) pigs from 161 collected sites (20.17%, 161/797) were seropositive for PRV-gE antibody. Though only 2.33% tissue samples were positive for PRV nucleic acids, all the representative PRV strains were variant. It was learned that most practitioners were frequently injured when working, the injured sites mainly included hand and foot. Among the three transmission routes of PRV, the aerosol transmission route was often overlooked. Moreover, the workers lacked self-protection awareness and were poor conscious about PRV and its potential threat to humans. All the results demonstrate that PRV remains widely spread in pig populations, while the potential threats of PRV in pig industry receive less attention, suggesting that targeted educational programs to these people should be performed.

Differentiation Between Chaenomelis Fructus and its Common Adulterant, Guangpi Mugua.

BACKGROUND: The dried fruit of Chaenomeles speciosa, known as Chaenomelis Fructus or Zhoupi Mugua, is a type of traditional Chinese medicine (TCM) that is widely used to treat many diseases. Guangpi Mugua, the dried fruit of the Chaenomeles sinensis, is its most commonly known adulterant. OBJECTIVE: To establish a robust approach for the quality control and identification of Chaenomelis Fructus. METHOD: Thin-layer chromatography (TLC) was optimized and used to discriminate Chaenomelis Fructus from Guangpi Mugua. High-performance liquid chromatography (HPLC) combined with fingerprint analysis and partial least-squares (PLS) discrimination analysis (DA) was employed to study the chemical differences between Chaenomelis Fructus and Guangpi Mugua. The single standard to determine multi-components (SSDMC) method, with credible precision, repeatability, stability, and durability, was developed for quantitative analysis of the abundant markers. RESULTS: The developed TLC and HPLC methods were effective in the authentication of Chaenomelis Fructus. Moreover, oleanolic acid, ursolic acid, pomolic acid, corosolic acid, 3-O-acetylpomolic acid, and one unknown compound were identified to be critical markers for the discrimination of Chaenomelis Fructus from Guangpi Mugua. CONCLUSION: Adulteration has always been a challenge in the development of TCM. This study presents useful insights that may help solve the problem of adulteration during the preparation of Chaenomelis Fructus. HIGHLIGHTS: The present study provides a systematic method for the quality control of Chaenomelis Fructus. This is therefore the first step towards solving the problem of adulteration to improve the clinical safety and effectiveness of Chaenomelis Fructus.

Advancement of Natural Compounds as Anti-rheumatoid Arthritis Agents: A Focus on Their Mechanism of Actions.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by infiltration of inflammatory cells, synovial hyperplasia, pannus formation and bone destruction. RA is associated with high incidence of disability worldwide. Although several anti-RA agents are available in the market, clinical use of these drugs is limited due to their severe side effects. Several studies are currently exploring new anti-rheumatic drugs which are more effective and have fewer side effects. Notably, natural products with anti-RA effect have been identified and studies have reported the underlying molecular mechanisms of action of the novel and known compounds. This review explored naturally occurring known and novel compounds that have anti-RA activity. Further, the compounds are classified based on their molecular mechanisms of action as anti-RA agents. In addition, the safety of compounds from natural sources is compared with that of conventional drugs. In addition, clinical trials for anti-RA compounds isolated from natural plant sources were summarized in this manuscript.

Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases. AIM OF THE STUDY: To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. MATERIALS AND METHODS: The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. RESULTS: The MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. CONCLUSIONS: This research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.

Transcriptomic and metabonomic profiling reveal the anti-obesity effects of Chikusetsusaponin V, a compound extracted from Panax japonicus.

OBJECTIVES: To explore the in vivo anti-obesity effect of chikusetsusaponin V and explore the underlying mechanism by transcriptomic and metabonomic methods. METHODS: The physiological parameters of high-fat-diet induced obese mice administered with or without 25 mg/kg and 100 mg/kg of chikusetsusaponin V by gavage for 16 weeks were recorded. In addition, the RNA-sequencing and UHPLC-Q-TOF techniques were applied to obtain the transcriptomic and metabolomic profiling, respectively. KEY FINDINGS: Chikusetsusaponin V could significantly alleviate the high-fat-diet induced increase in the weight of the whole body and obesity-related organs or tissues, and ameliorate the lipid content in the blood, the lipid accumulation in the livers, as well as the hypertrophy of the fat tissues. Importantly, transcriptomic results revealed that more than 30 genes involved in the pathway which closely associates with obesity, were significantly altered. Moreover, metabolomic data indicated the key differential metabolites enriched in the pathways such as the activated protein kinase signaling pathway which is a vital mediator of obesity and other processes. CONCLUSIONS: The integrative analysis highlighted that chikusetsusaponin V significantly influenced the activated protein kinase signaling pathway at both transcriptomic and metabolomic levels, thereby exerting anti-obesity effects.

HPLC-Based Qualitative and Quantitative Analyses of Alkaloids in Chewable Areca Products from Different Geographic Regions.

BACKGROUND: Chewable areca products are popular in Asian countries, including India, Pakistan, Malaysia, and China. The major alkaloids present in areca products are guvacine, arecaidine, guvacoline, and arecoline which cause carcinogenicity and addiction. OBJECTIVE: The objective of this study was the quantitative analysis of the alkaloid content of areca chewable products from different countries and regions using HPLC-UV, as well as the benefit of their safety evaluation products. METHOD: An HPLC-UV method was established for qualitative and quantitative analyses of 65 batches of areca chewable products from different countries and regions. Additionally, similarity evaluation of chromatographic fingerprints was applied for data analysis. RESULTS: These results reveal a significant variation in the levels of areca alkaloids among tested products, specifically guvacoline (0.060-1.216 mg/g), arecoline (0.376-3.592 mg/g), guvacine (0.028-1.184 mg/g), and arecaidine (0.184-1.291 mg/g). There were significant differences in the alkaloid content of areca chewable products from different producing areas. CONCLUSIONS: The method will be useful in the safety evaluation of different areca chewable products. HIGHLIGHTS: The established HPLC-UV method can be adopted for safety evaluation of areca chewable products from different countries and regions due to its general applicability.

Recent Development on Anti-Obesity Compounds and their Mechanisms of Action: A Review.

Obesity, associated with a series of complications such as diabetes, hypertension, and heart disease, is a great threat to human health and leads to increased morbidity and mortality. Despite the presence of anti-obesity agents on the market, the application of these drugs is limited because of their typical side effects. More effective and safe weight-loss drugs are being pursued by many researchers, correspondingly, growing small molecules and natural products with anti-obesity effects have been identified and the molecular mechanisms underlying the action of the novel and known compounds have at least partially been revealed. Therefore, the field does witness great progress year by year. In this review, we intend to provide a comprehensive and updated view on the known and novel compounds which possess anti-obesity effects and further classify them according to the molecular mechanisms of their actions in regulating the major anti-obesity pathways.