Integration of metabolomics and network pharmacology to validate the mechanism of Schisandra chinensis（Turcz.）Baill - Acorus tatarinowii Schott ameliorating the Alzheimer's disease by regulating the aromatase activity to affect local estrogen in brain of AD model rats

Alzheimer's disease (AD) is a latent and progressive neurodegenerative disease. Schisandra chinensis（Turcz.）Baill - Acorus tatarinowii Schott (Sc-At) are effective in treating neurological disorders.Purpose of this study is to explore the mechanism of Sc-At in AD treatment. First, untargeted ultra-performance liquid chromatography quadrupole-time of flight/mass spectrometer (UPLC-QTOF/MS) metabolomics was employed to detect the rat brain metabolism. Then, network pharmacology was used to determine the potential anti-AD targets. Bioinformatics, and molecular docking were conducted for further analysis. A MetScape study examined the association between differential metabolites and potential targets. Finally, the targeted ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) metabolomics and the potential protein activity studies were carried out to elucidate the mechanisms. The results showed that Sc-At improved the neuronal cell alignment disorder in hippocampal CA1 region of AD rats. In brain metabolomics, 30 differential metabolites were screened in the study model versus blank group. The network pharmacology analyzed 54 targets of Sc-At anti-AD where, 14 were correlated with amyloid β-protein (Aβ). Aromatase was selected as an important hub target having the best binding power in molecular docking simulation predictions and also correlated with Aβ. Further tests showed that the brain aromatase activity, and the downstream product 17β-Estradiol levels were elevated in AD rats treated with Sc-At. This work may provide new perspectives for the pharmacological effects and the action mechanisms of natural compounds extracts in treating AD progression.     

Camellia sinensis: Insights on its molecular mechanisms of action towards nutraceutical,anticancer potential and other therapeutic applications

The Camellia sinensis plant provides a wide diversity of black, green, oolong, yellow, brick dark, and white tea. Tea is one of the majorly used beverages across the globe, succeeds only in the water for fitness and pleasure. Generally, green tea has been preferred more as compared to other teas due to its main constituent e.g. polyphenols which contribute to various health benefits. The aim of this updated and comprehensive review is to bring together the latest data on the phytochemistry and pharmacological properties of Camellia sinensis and to highlight the therapeutic prospects of the bioactive compounds in this plant so that the full medicinal potential of Camellia sinensis can be realised. A review of published studies on this topic was performed by searching PubMed/MedLine, Scopus, Google scholar, and Web of Science databases from 1999 to 2022. The results of the analysed studies showed that the main polyphenols of tea are the four prime flavonoids catechins: epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), and epicatechin (EC) along with the beneficial biological properties of tea for a broad heterogeneity of disorders, including anticancer, neuroprotective, antibacterial, antiviral, antifungal, antiobesity, antidiabetes and antiglaucoma activities. Poor absorption and low bioavailability of bioactive compounds from Camellia sinensis are limiting aspects of their therapeutic use. More human clinical studies and approaching the latest nanoformulation techniques in nanoparticles to transport the target phytochemical compounds to increase therapeutic efficacy are needed in the future.     

An integrated strategy of secondary metabolomics and glycomics to investigate multi-component variations in wine-processing of medicinal herbs and functional foods: A case study on Fructus Corni

Fructus Corni (FC), as a promising Chinese medicinal herb, has aroused considerable interest. Generally, FC needs to be processed according to the limited standard policy in China before clinical application, while the investigations on the specific processing methods (such as wine steaming or high-pressure wine steaming) are unclear. A comprehensive metabolomics strategy based on integrated non-targeted metabolomics and targeted glycomics in this paper was implemented to investigate the influences of the different processing technologies such as steaming, wine steaming, high-pressure steaming, high-pressure wine steaming, wine immersion, and wine stir-frying on FC, respectively. UHPLC-Q-TOF-MS/MS was employed for identifying and distinguishing the secondary metabolites. A total of 85 components were identified in all groups. The results of PCA score plots showed that the crude and processed samples had a complete separation, and wine steamed and high-pressure wine steamed samples could be a category, indicating that the two processed products had a similar quality. Multiple chromatography including HPLC (C₁₈)-PDA, HPLC (NH₂)-ELSD, and HPGPC-ELSD was used for determining the molecular weight distributions, the monosaccharide compositions of polysaccharides, and the contents of free monosaccharides and oligosaccharides. The results indicated that the content and composition of saccharides were different in crude and different processed FC. The polysaccharides were composed of fucose, arabinose, galactose, glucose, galacturonic acid, mannose and rhamnose, and the free monosaccharides were composed of fucose, arabinose, galactose, glucose, mannose, rhamnose and fructose in all FC samples. The PCA score plots of the glycomics indicated that the crude and high-pressure wine steamed FC could be a category, showing that the two groups had similar chemical compositions. Ultimately, the simulation processing experiments indicated that the transformation of morroniside, polysaccharides, oligosaccharides, fructose, and glucose to 5-HMF through the reactions of dehydration and deglycosylation was the potential mechanism of enhancing the effects by processing. Conclusionly, the saccharides should be investigated as thoroughly as the secondary metabolites, and the high-pressure wine steamed FC could be an alternative to wine steamed FC.     

Integrating approach to discover novel bergenin derivatives and phenolics with antioxidant and anti-inflammatory activities from bio-active fraction of Syzygium brachythyrsum

Syzygium brachythyrsum is an important folk medicinal and edible plant in Yunnan ethnic minority community of China, however, little is known about the chemical and bio-active properties. The present study is aimed to identify the bioactive constituents with antioxidant and anti-inflammatory properties by an integrating approach. First, two new bergenin derivatives, brachythol A (1) and brachythol B (2), together with eleven known phenolic compounds (3–13) were isolated from bioactive fractions by phytochemical method. Among these isolated chemicals, five bergenin derivatives, along with 3 phenolics were found in Syzygium genus for the first time. Then, a further chemical investigation based on ultra-high-performance liquid chromatography-Q Exactive Orbitrap mass spectrometry resulted in a total of 107 compounds characterized in the bio-active fractions, including 50 bergenin derivatives, among which 14 bergenin derivatives and 14 phenolics were potential new natural chemicals. Most of the isolated compounds showed obvious antioxidant activities, while compounds 11, 12, and 13 had favorable performance. Eight compounds (2–5, 7, and 9–11) showed good inhibitory activity on nitric oxide (NO) production in macrophage RAW 264.7 cells. The structure–activity correlation analysis indicated that the antioxidation and anti-inflammatory activities enhanced when bergenin was esterified with gallic acid, caffeic acid or ferulic acid. This is the first report of bergenins in Syzygium genus and the richness in new bio-active bergenins and gallic acid derivatives indicated that Syzygium brachythyrsum is a promising functional and medicinal resource.     

Phytochemical prospection,evaluation of antibacterial activity and toxicity of extracts of Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz

Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz is a arboreal species found in the Caatinga from Northeast of Brazil that has been used in popular medicine as an anti-inflammatory, healing, analgesic and for the treatment of respiratory system disorders. Therefore, the objective of this work was to evaluate the composition of ethanol extracts from the leaves and inner bark of Libidibia ferrea, as well as to verify its antibacterial activity and as a potential inhibitor of the TetK efflux pump in Staphylococcus aureus strains, in addition to investigating the toxicity of the extracts in a Drosophila melanogaster model. The analysis and quantification of the extracts markers was performed by High Performance Liquid Chromatography (HPLC). To determine the Minimum Inhibitory Concentration (MIC) broth microdilution tests were carried out. The evaluation of efflux pump inhibition was performed by modifying the MIC of antibiotics and ethidium bromide. Mortality and negative geotaxis tests were used to verify the toxicity of extracts on D. melanogaster. Hydrolysable tannins (gallic acid and ellagic acid) and flavonoids were found in HPLC analysis. The extracts did not show antibacterial activity, demonstrating a MIC ≥ 1024 µg/mL, however the ethanolic extract of the leaves decreased the MIC of the antibiotic from 64 µg/mL to 16 µg/mL, but this effect is not associated with the inhibition of the efflux pump. The extracts did not show toxicity in a D. melanogaster model. This is the first study to evaluate the antibacterial activity of L. ferrea extracts on the IS-58 strain of S. aureus, as well as the first to investigate its toxicity using D. melanogaster. From the results, further studies are needed to determine the mechanisms of action of the extract with other antibiotics.     

Chemical composition,antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile,study in vitro and in silico

Chilean Laureliopsis philippiana has been used in traditional medicine by the Mapuche and their ancestors. To evaluate its pharmacological activity, Laureliopsis philippiana leaf essential oil extract (LP_EO) was chemically and biologically characterized in the present study. In vitro antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and tumor cell culture lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the essential oil was analyzed using gas chromatography–mass spectrometry. The oil contains six major monoterpenes: eucalyptol (27.7 %), linalool (27.6 %), isozaphrol (19.5 %), isohomogenol (12.6 %), α-terpineol (7.7 %), and eudesmol (4.8 %). Based on quantum mechanical calculations, isosafrole and isohomogenol conferred in vitro antioxidant and antimicrobial activity to LP_EO. In addition, LP_EO showed antimicrobial activity against clinical Helicobacter pylori isolates (MIC 64 and MBC > 128 μg·mL^?1), Staphylococcus aureus (MIC 32 and MBC > 64 μg·mL^?1), Escherichia coli (MIC 8 and MBC 16 μg·mL^?1) and Candida albicans (MIC 64 and > 128 μg·mL^?1). LP_EO could selectively inhibit the proliferation of epithelial tumor cell lines but showed low toxicity against Caenorhabditis elegans (0.39 to 1.56 μg·mL^?1). Therefore, LP_EO may be used as a source of bioactive compounds in novel pharmacological treatments for veterinary and human application, cosmetics, or sanitation.     

Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation

Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion.     

New mechanistic insights on Justicia vahlii Roth: UPLC-Q-TOF-MS and GC–MS based metabolomics,in-vivo,in-silico toxicological,antioxidant based anti-inflammatory and enzyme inhibition evaluation

Justicia vahlii Roth. (acanthaceae) is an important medicinal food plant used in pain relief and topical inflammation. The present study aimed to evaluate phytochemical composition, toxicity, anti-inflammatory, antioxidant and enzyme inhibition potential of n-butanol extract of J. vahlii (BEJv). The extract prepared through maceration was found rich in total phenolic contents (TPC) 196.08 ± 6.01 mg of Gallic acid equivalent (mg GAE/g DE) and total flavonoid contents (TFC) 59.08 ± 1.32 mg of Rutin equivalent (mg RE/g DE). The UPLC-Q-TOF-MS analysis of BEJv showed tentative identification of 87 compounds and 19 compounds were detected in GC–MS analysis. The HPLC-PDA quantification showed the presence of 14 polyphenols amongst which kaempferol (3.45 ± 0.21 µg/ mL DE) and ferulic acid (2.31 ± 1.30 µg/ mL DE) were found in highest quantity. The acute oral toxicity study revealed the safety and biocompatibility of the extract up to 3000 mg/kg in mice. There was no effect of BEJv on human normal liver cells (HL 7702) and very low cytotoxic effect on liver cancer cells (HepG2) and breast cancer cells (MCF-7). In anti-inflammatory evaluation, the BEJv treated groups showed significant inhibition (p < 0.001) of late phase carrageenan induced paw edema at 400 mg/kg and increased the levels of oxidative stress markers; catalase, superoxide dismutase (SOD) and glutathione (GSH) while decreased the inflammatory markers; interleukin-1beta (IL-β) and tumor necrosis factor alpha (TNF-α) in paw tissue of mice. BEJv displayed highest results in Ferric reducing antioxidant power (FRAP) assay 97. 21 ± 2.34 mg TE (trolox equivalent)/g DE, and highest activity 3.32 ± 0.31 mmol ACAE (acarbose equivalent)/g D.E against α-glucosidase. Docking study showed good docking score by the tested compounds against the various clinically significant enzymes. Conclusively the current study unveiled J. vahlii as novel non-toxic source with good antioxidant-mediated anti-inflammatory potential which strongly back the traditional use of the species in pain and inflammation.     

Antibacterial activity of flavonoids and triterpenoids isolated from the stem bark and sap of Staudtia kamerunensis Warb. (Myristicaceae)

The chemical investigation of the ethyl acetate extract of the stem bark of Staudtia kamerunensis and sap led to the isolation of six compounds which included three isoflavonoids: biochanin A (1), formononetin (2) and 3-(1,3-benzodioxol-5-yl)-5,6,7-trimethoxy-4H-1-benzopyran-4-one (3), one flavonoid: (-) epicatechin (4) and two pentacyclic triterpenoids (oleanan-12-ene-2α,3β -diol (5) and 2α,3β-dihydroxylup-20-ene (6). They were characterized by HREIMS (High Resolution Electron Ionisation Mass Spectrometry), NMR spectroscopy (1D and 2D) and comparison with existing data in literature. The crude extract and isolates were tested against twelve bacterial strains namely; Bacillus subtilis, Staphylococcus epidermidis, Enterococcus faecalis, Mycobacterium smegmatis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Proteus mirabilis and Klebsiella pneumonia. Streptomycin, nalidixic acid and ampicillin were used as standard antibacterial drugs. The results revealed significant antibacterial activity for both the ethyl acetate partition and for the tested compounds, with the lowest MIC value being 15.625 μg/mL. A synergistic activity of the isolated triterpenoids was evaluated with interesting results. On a general note, the antibacterial activity of compound 5 was doubled specifically against Gram-negative bacterial strains. This could be a therapeutic antimicrobial pathway in face of the rising bacterial resistance. To the best of our knowledge, it is the first time that flavonoids and triterpenoids are isolated from this genus and species. It is also the first report of antibacterial studies on this species.     

Unraveling the mystery of efficacy in Chinese medicine formula: New approaches and technologies for research on pharmacodynamic substances

Traditional Chinese medicine (TCM) is the key to unlock treasures of Chinese civilization. TCM and its compound play a beneficial role in medical activities to cure diseases, especially in major public health events such as novel coronavirus epidemics across the globe. The chemical composition in Chinese medicine formula is complex and diverse, but their effective substances resemble “mystery boxes”. Revealing their active ingredients and their mechanisms of action has become focal point and difficulty of research for herbalists. Although the existing research methods are numerous and constantly updated iteratively, there is remain a lack of prospective reviews. Hence, this paper provides a comprehensive account of existing new approaches and technologies based on previous studies with an in vitro to in vivo perspective. In addition, the bottlenecks of studies on Chinese medicine formula effective substances are also revealed. Especially, we look ahead to new perspectives, technologies and applications for its future development. This work reviews based on new perspectives to open horizons for the future research. Consequently, herbal compounding pharmaceutical substances study should carry on the essence of TCM while pursuing innovations in the field.     

Basic characterization and Alzheimer’s disease relieving property of a glucose riched polysaccharide from Cibotium barometz

The water-soluble polysaccharides from plants have attracted ever-increasing attention in the field of food and drug due to their various activities and low toxicity. CBP50-1, as a purified fraction of polysaccharide from the rhizome of Cibotium barometz (CBP), mainly consisted of glucose (55.45%) and xylose (25.27%). CBP50-1 showed excellent antioxidant activity for scavenging 2,2?Diphenyl?1?picryl?hydrazy (DPPH) radical and hydroxyl radical, further inhibiting lipid peroxidation. CBP50-1 significantly improved the survival rate of Caenorhabditis elegans under thermal and oxidative stress. Furthermore, CBP50-1 reduced the paralysis and oxidative damage induced by amyloid-beta (Aβ) and increased the antioxidant enzyme activity in Alzheimer’s disease (AD) model C. elegans CL4176 through c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signal pathway. Thus, CBP50-1 had a potential application in health industries.     

Production of bioactive compounds from callus of Pueraria thomsonii Benth with promising cytotoxic and antibacterial activities

For thousands of years Pueraria thomsonii Benth has been used to treat a number of diseases in traditional Chinese pharmacopeia. Despite these uses, there is still insufficient information on its biological activity and chemical composition. In this respect, the in vitro callus culture of P. thomsonii was subjected to identify anticancer and antibacterial compounds. Based on significant preliminary cytotoxicity and antibacterial activities; the chemical investigation led to the isolation of isoflavonoids, coumaric acid derivative and dihydroxyflavanone-type of compounds viz., daidzin (1), puerarin (2), biochanin A (3), daidzein (4), p-coumaric acid ethyl ester (5) and liquiritigenin (6), respectively. These compounds were tested for their cytotoxicity and antibacterial activities. Among them, p-coumaric acid ethyl ester (5) exhibited significant cytotoxicity with GI₅₀ values of 14.73, 15.64 and 20.88 μM/mL against 4T1, NC1-H1975 and A549, respectively; the other isoflavones and aflavonoid showed moderate to weak activities. Moreover, p-coumaric acid ethyl ester (5) inhibited the growth of K. pneumonia, MRSE and MRSA at very low MIC values of 6.01, 12.01 µg/mL 24.02, respectively. On the other hand compounds biochanin A (3) and liquiritigenin (6) showed moderate antibacterial activity. Because of the potential anticancer and antibacterial activities of bioactive compounds from P. thomsonii, they can be used to treat various cancer and emerging bacterial infections.     

Chemical profiling of Verbena officinalis and assessment of its anti-cryptosporidial activity in experimentally infected immunocompromised mice

Cryptosporidiosis is a global zoonotic infection that causes water-borne epidemics of diarrhea. Nevertheless, there are few available therapies for cryptosporidiosis. However, the gold standard drug nitazoxanide (NTZ) has limited efficacy in malnourished and immunocompromised patients. Furthermore, Verbena officinalisL. is a herbal plant widely used in traditional medicine to cure several health disorders and is recognized to possess numerous therapeutic applications. In the present study, the phytochemical composition of aerial part extract from Verbena officinalis was investigated via LC-ESI-MS/MS.Furthermore, the anti-cryptosporidial activity was also performed using an animal model. Fifty mice were divided into 5 groups; GI: non-infected (Negative control), GII: infected non treated (positive control), GIII: infected, treated with NTZ, GIV: infected, treated with V. officinalis n-butanol extract, GV: infected, treated with a combination of NTZ and V. officinalis. Parasitological examination revealed a highly significant difference (P-value < 0.001) between GIII, GIV, and GV compared to GII regarding the mean number of Cryptosporidium spp. oocyst in the stool. Moreover, GV showed the best efficacy with a percentage of 87%. Also, histopathological examination showed variable degrees of improvement in the villous broadening, and the inflammatory infiltrates in the small intestine with a reduction of hepatocyte degeneration and mononuclear infiltration in GIII, GIV, and GV compared to GII, with the best results seen in GV. Additionally, the chemical profiling of n-butanol extract identified 16 secondary metabolites comprising flavonoids, phenolic acids, phenylethanoids, and coumarins. In conclusion, V. officinalis is an intrinsic supplier of biologically active metabolites with outstanding anti-parasitic and possible anti-inflammatory effects.     

Pitanga (Eugenia uniflora L.) as a source of bioactive compounds for health benefits: A review

The pitangueira (Eugenia uniflora) is a tree native to Brazil but is cultivated in several subtropical countries. A great diversity of nutrients and bioactive compounds have been found in the leaves and fruits of E. uniflora, which supports its use in folk medicine to treat diseases such as stomach and intestinal disorders, fever and general inflammation. Antimicrobial, antiviral, antifungal and antioxidant effects on metabolism have been reported for this plant. This review discusses the phytochemical profile, toxicity and pharmacological action of E. uniflora leaves and fruits and points out that gaps in the literature that need to be investigated further. This review also discusses studies developed with E. uniflora demonstrating its promising therapeutic potential for several diseases with an apparent low toxicity in mammals. The compilation of the main pharmacological and toxicological results, as well as the phytochemical characterization of the varieties and constituents of E. uniflora are general aspects that this review attempts to demonstrate in order to contribute to the new approaches and developments to plant-derived natural product drug discovery. However, further studies are required to establish the nutraceutical effects and uses of E. uniflora as an important and safe supplement for human health.     

Polymeric microspheres as support to co-immobilized Agaricus bisporus and Trametes versicolor laccases and their application in diazinon degradation

The laccase enzymes of Agaricus bisporus and Trametes versicolor were successfully covalently co-immobilized on poly(glycidyl methacrylate) microspheres. The enzyme load reached after the co-immobilization of both enzymes was 6.75 U g⁻¹ carrier. The resulting biocatalyst showed the combined properties of both immobilized enzymes, increasing their optimum pH and temperature ranges. The storage and operational stabilities were also improved after co-immobilization. In presence of mediator (ABTS) the organophosphate pesticide diazinon was 100% biodegraded after 48 h of reaction with 0.2 U/mL of co-immobilized enzymes (at the two maximum activity pH values: 2.0 and 3.0). In the absence of a mediator, the degradation percentages were above 88%. Data showed that, compared with single enzymatic immobilization, the co-immobilization of the two laccases is an easy, efficient, and low cost alternative to expanding the range of work of the biocatalyst, thereby improving the stability and some biochemical properties to generate a powerful alternative for pesticide degradation in a wide range of conditions.     

Eco-friendly synthesis of size-controlled silver nanoparticles by using Areca catechu nut aqueous extract and investigation of their potent antioxidant and anti-bacterial activities

Silver nanoparticles (AgNPs) have attracted considerable attention owing to their unique biological applications. AgNPs synthesized by plant extract is considered as a convenient, efficient and eco-friendly material. In this work, the aqueous extract of Areca catechu L. nut (ACN) was used as the reducing and capping agents for one-pot synthesis of AgNPs, and their antioxidant and antibacterial activities were investigated. UV (Ultra Violet)-visible spectrum and dynamic light scattering (DLS) analysis revealed that the size of AgNPs was sensitive to the synthesis conditions. The synthesized AgNPs were composed of well-dispersed particles with an small size of about 10 nm under the optimal conditions (pH value of extract was 12.0; AgNO₃ concentration was 1.0 mM; reaction time was 90 min). In addition, scanning electron microscope with energy dispersive X-ray (SEM-EDX), transmission electron microscopy (TEM) and X-ray diffraction (XRD) results further verified that the synthesized AgNPs had a stable and well-dispersed form (Zeta potential value of ?30.50 mV and polydispersity index of 0.328) and a regular spherical shape (average size of 15–20 nm). In addition, Fourier transform infrared spectrometry (FTIR) results revealed that phytochemical constituents in ACN aqueous extract accounted for Ag⁺ ion reduction, capping and stabilization of AgNPs. The possible reductants in the aqueous extract of Areca catechu L. nut were identified by high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (HPLC-ESI-qTOF/MS) method. More importantly, the synthesized AgNPs indicated excellent free radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH, IC₅₀ = 11.75 ± 0.29 μg/mL) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS⁺, IC₅₀ = 44.85 ± 0.37 μg/mL), which were significant higher than that of ascorbic acid. Moreover, AgNPs exhibited an enhanced antibacterial activity against six selected common pathogens (especially Escherichia coli and Staphylococcus aureus) compared with AgNO₃ solution. In a short, this study showed that the Areca catechu L. nut aqueous extract could be applied for eco-friendly synthesis of AgNPs.     

Metabolomic-based investigation of Yinlan alleviating hyperlipidemia by inhibiting blood stasis and phlegm turbidity through the PXR-CYP3A4-ABCB1-FXR pathway

Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL.     

Traditional uses,phytochemistry, pharmacology and other potential applications of Vitellaria paradoxa Gaertn. (Sapotaceae): A review

Vitellaria paradoxa Gaertn. is a multipurpose medicinal plant of the family Sapotaceae, and it has been widely used usually in the clinical traditional medicine as remedy for a wide range of diseases for several decades. In addition, the plant has also found applications in confectionery, cosmetics and soaps, and pharmaceuticals both locally and internationally. V. paradoxa, which has been identified with >150 phytoconstituents, is rich in oleanane-type triterpene acids and glycosides, such as paradoxosides A-E, tieghemelin A, parkiosides A-C, bassic acid, as well as flavonoids such as quercetin and catechin-type compounds. The extracts and the active constituents of V. paradoxa have been investigated for various pharmacological activities, including but not limited to anticancer, melanogenesis-inhibitory, antibacterial, anti-diabetic, antioxidant, anti-inflammatory, anti-diarrhoeal, and antifungal activities. Additionally, V. paradoxa has also been utilized in nanoparticles (NPs) synthesis. These NPs among other things have shown significant antinociceptive and antiedematogenic activities as well as environmental friendly adsorptive properties for the removal of pollutants from pharmaceutical effluents. Overall, this review comprehensively examines the traditional uses, phytochemistry, pharmacology, toxicology, clinical studies, and nanoparticles synthesized from V. paradoxa and their applications.     

Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism

Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products.     

The ethnobotanical,phytochemistry and pharmacological activities of Psidium guajava L.

Psidium guajava L., commonly known as guava is an important tropical food plant with diverse medicinal values. In traditional medicine, it is used in the treatment of various diseases such as diarrhoea, diabetes, rheumatism, ulcers, malaria, cough, and bacterial infections. The aim of this review is to provide up-to-date information on the ethnomedicinal uses, bioactive compounds, and pharmacological activities of P. guajava with greater emphasis on its therapeutic potentials. The bioactive constituents extracted from P. guajava include phytochemicals (gallic acid, casuariin, catechin, chlorogenic acid, rutin, vanillic acid, quercetin, syringic acid, kaempferol, apigenin, cinnamic acid, luteolin, quercetin-3-O-α-L-arabinopyranoside, morin, ellagic acid, guaijaverin, pedunculoside, asiastic acid, ursolic acid, oleanolic acid, methyl gallate and epicatechin) and essential oils (limonene, trans-caryophyllene, α-humulene, γ-muurolene, selinene, caryophyllene oxide, bisabolol, isocaryophyllene, δ-cadinene, α-copaene, α-cedrene, β-eudesmol, α-pinene, β-pinene, β-myrcene, linalool, α-terpineol and eucalyptol). In vitro and in vivo studies demonstrated that P. guajava possesses pharmacological activities such as antidiabetic, antidiarrhoeal, hepatoprotective, anticancer, antioxidant, anti-inflammatory, antiestrogenic, and antibacterial activities which support its traditional uses. The exhibited pharmacological activities reported may be attributed to the numerous bioactive compounds present in different parts of P. guajava. Based on the beneficial effects of P. guajava as well as its bioactive constituents, it can be exploited in the development of pharmaceutical products and functional foods. However, there is a need for comprehensive studies in clinical trials to establish the safe doses and efficacy of P. guajava for the treatment of several diseases.