Active Ingredients Research Articles

Network Pharmacology Prediction and Molecular Docking-based Strategy to Explore the Potential Mechanism of Guiyi Tonglong Prescription in the Treatment of Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia (BPH) is a common condition affecting the urinary tract. This study aimed at exploring the potential of Guiyi Tonglong (GYTL) prescription for the treatment of benign prostatic hyperplasia using network pharmacology and molecular docking technology. Methods: The main active ingredients in GYTL prescription were identified from the Traditional Chinese Medicine Systems Pharmacology and the Integrative Pharmacology-based Traditional Chinese Medicine (TCMIP) databases based on drug similarity of ≥ 30% and oral bioavailability of ≥ 0.18. Protein–protein interaction (PPI) networks, gene ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to study the interactions and pathway enrichment and establish ingredient-target-pathway networks. The structure of the active ingredient was docked to that of the potential protein target using the AutoDock molecular docking software. Results: A total of 86 active ingredients and 130 potential targets were screened from GYTL prescription, and a PPI network was constructed to identify the five most important core targets, namely SRC, TP53, STAT3, AKT1, and PIK3CA. Enrichment analysis revealed that GYTL prescription may play a role in the treatment of BPH through multiple signaling pathways, such as PI3K-Akt, EGFR, AGE-RAGE, and HIF-1. Molecular docking indicated a potential interaction between the active ingredients and targets. Conclusion: These results provide further information regarding the active ingredients and molecular mechanisms of GYTL prescription in treating BPH.

Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy

Globally, nearly half of all pregnancies are unintended, ∼1.3 million new human immunodeficiency virus (HIV) infections are reported every year, and more than 500 million people are estimated to have a genital herpes simplex virus (HSV-2) infection. Here we report the first 3D printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for prevention of HIV, HSV-2, and unintended pregnancy. The IVRs were fabricated using state-of-the-art Continuous Liquid Interface Production (CLIP™) 3D printing technology using a biocompatible silicone-urethane based resin. Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue. All three active pharmaceutical ingredients (APIs) were loaded in the IVR using a single-step drug loading process driven by absorption. DPV, PTV, and LNG elicited zero-order release kinetics in vitro in simulated vaginal fluid (SVF) at pH 4 and pH 8 relevant to human and macaque vaginal pH respectively. CLIP 3D printed MPT IVRs remained stable after 6 months of storage at 4 °C with no change in physical, dimensional, or mechanical properties and no change in drug concentration and absence of drug degradation byproducts. The MPT IVRs elicited sustained release of all three APIs in macaques for 28 days with median plasma concentrations of 138 pg/mL (DPV), 18,700 pg/mL (PTV), and 335 pg/mL (LNG). Safety studies demonstrated that the MPT IVRs were safe and well tolerated in the macaques with no observed change or abnormalities in vaginal pH and no significant changes in any of the 22 mucosal cytokines and chemokines tested including pro-inflammatory (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, IL-17, IL-18) and anti-inflammatory (IL-10, IL-12) cytokines while the MPT IVR was in place or after its removal. Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy and two highly prevalent sexually transmitted infections (STIs).

Uncovering the effects and mechanisms of tea and its components on depression, anxiety, and sleep disorders: A comprehensive review

Depression, anxiety and sleep disorders are prevalent psychiatric conditions worldwide, significantly impacting the physical and mental well-being of individuals. The treatment of these conditions poses various challenges, including limited efficacy and potential side effects. Tea, a globally recognized healthful beverage, contains a variety of active compounds. Studies have shown that consuming tea or ingesting its certain active ingredients have a beneficial impact on the mental health issues mentioned above. While the effects of tea on physical health are well-documented, there remains a gap in our systematic understanding of its impact on mental health. This article offers a thorough overview of animal, clinical, and epidemiological studies examining tea and its components in the treatment of depression, anxiety, and sleep disorders, and summarizes the associated molecular mechanisms. The active ingredients in tea, including L-theanine, γ-aminobutyric acid (GABA), arginine, catechins, theaflavins, caffeine, theacrine, and several volatile compounds, may help improve depression, anxiety, and sleep disorders. The underlying molecular mechanisms involve the regulation of neurotransmitters, including monoamines, GABA, and brain-derived neurotrophic factor (BDNF), as well as the suppression of oxidative stress and inflammation. Additionally, these ingredients may influence the microbiota-gut-brain (MGB) axis and the hypothalamic–pituitary–adrenal (HPA) axis. This review provides valuable insights into the effects and mechanisms by which tea and its components regulate depression, anxiety, and sleep disorders, laying the groundwork for further research into relevant mechanisms and the development of tea-based mental health products.

Exploration of the key active ingredients and mechanisms of Sparganii Rhizoma-Curcumae Rhizoma compatible formulation against human colorectal cancer through network pharmacology and in vitro experiments

IntroductionSparganii Rhizoma-Curcumae Rhizoma (SR-CR) formulation may offer an effective treatment for human colorectal cancer (CRC). However, the active ingredients and underlying mechanisms of this herbal formulation remain unclear. MethodsThis study integrates network pharmacology, molecular docking and experimental verification to identify key active ingredients and elucidate the mechanisms of SR-CR in CRC treatment. ResultsTwenty-three active components of SR-CR were identified using the TCMSP, UniProt and Gene Cards databases. These components were associated with 178 targets, of which 118 are directly related to CRC. Protein-protein interaction (PPI) network analysis identified protein kinase B (AKT) 1, epidermal growth factor receptor (EGFR), SRC, Bcl2 and CASP3 as core anti-CRC targets. Gene Ontology (GO) and KEGG pathway analyses were performed on these 178 intersecting targets, and the results showed that these targets are involved in EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications. At the same time, five compounds, including bisdemethoxycurcumin, formononetin, β-sitosterol, stigmasterol and hederagenin, were selected based on the target number of effective components and tested for cytotoxicity against human CRC cell lines HT-29, HCT-8 and HCT-116 in vitro. The results showed that bisdemethoxycurcumin exhibited significant anti-proliferative activity against HCT-116 cells. Molecular docking results indicated that bisdemethoxycurcumin effectively binds with AKT, EGFR, Bcl-2 and CASP3. Further pharmacological experiments demonstrated that bisdemethoxycurcumin inhibits HCT-116 cell proliferation and migration via inhibiting EGFR-AKT pathway, and induces apoptosis by up-regulating Bcl-2 expression. DiscussionBased on our study, inhibiting the EGFR-AKT pathway and upregulating Bcl2 may be one of the mechanisms by which SR-CR inhibits the growth of CRC. The main active ingredients of SR-CR include bisdemethoxycurcumin, formononetin, β-sitosterol, stigmasterol and hederagenin, which may exert anti-colon cancer activity by targeting the regulation of AKT, EGFR, Bcl-2 and CASP3. However, we need more in vitro and in vivo evidence to confirm this conclusion. This study lays the foundation for further research on the pharmacological mechanism of SR-CR in the treatment of CRC.

Mapping active pharmaceutical ingredients Distributions in tablets using Time-of-Flight secondary ion mass spectrometry with multivariate curve resolution

This study introduces an advanced approach to identifying signals associated with indapamide, amlodipine, and perindopril in solid dosage form using time-of-flight secondary ion mass spectrometry (ToF-SIMS) combined with multivariate curve resolution (MCR). The primary objective was to obtain and characterize these signals through MCR factors, which then led to identifying unique signals specific to each active pharmaceutical ingredient (API). These unique signals were crucial for constructing detailed 2D and 3D images of the API distribution within the tablet. The results demonstrated that indapamide and amlodipine exhibited multiple unique peaks, while perindopril had only one. Additionally, the study revealed non-homogeneous distribution patterns of APIs and excipients, such as SiO2 and Mg stearate. This work highlights the significance of applying advanced analytical techniques such as ToF-SIMS and MCR in the pharmaceutical field to ensure consistent therapeutic efficacy through a better understanding of API distribution.

Therapeutic Correlation of TLR-4 Mediated NF-κB Inflammatory Pathways in Ischemic Injuries.

Ischemia-reperfusion (I/R) injury refers to the tissue damage that happens when blood flow returns to tissue after a period of ischemia. I/R injuries are implicated in a large array of pathological conditions, such as cerebral, myocardial, renal, intestinal, retinal and hepatic ischemia. The hallmark of these pathologies is excessive inflammation. Toll-like receptors (TLRs) are recognized as significant contributors to inflammation caused by pathogens and, more recently, inflammation caused by injury. TLR-4 activation initiates a series of events that results in activation of nuclear factor kappa-B (NF-κB), which stimulates the production of pro-inflammatory cytokines and chemokines, exacerbating tissue injury. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the TLRs signalling pathway and the role of TLR-4/NF-κB in the pathophysiology of I/R injuries. Furthermore, this review highlights the various pharmacological agents (TLR-4/NF-κB inhibitors) with special emphasis on the various ischemic injuries (cerebral, myocardial, renal, intestinal, retinal and hepatic). Future research should prioritise investigating the specific molecular pathways that cause TLR-4/NF-κBmediated inflammation in ischemic injuries. Additionally, efforts should be made to enhance treatment approaches in order to enhance patient outcomes.

Insights into the anticancer effects of galangal and galangin: A comprehensive review

BackgroundsCancer continues to be the leading cause of death worldwide, significantly impacting both health and the economy. Natural products have emerged as promising sources for the development of new anticancer drugs, with galangal and their active ingredient, galangin, garnering substantial interest. PurposeThis study summarizes recent findings on the anticancer properties of galangal and galangin, highlighting their potential to target various cancer types. MethodsWe systematically searched the literature across PubMed, Web of Science, and Google Scholar, using keywords such as “Alpinia officinarum,” “Alpinia galanga”, “galangal,” and “galangin.” This thorough approach allowed us to gather and compile a comprehensive collection of existing research on the topic. ResultsThis article provided a thorough analysis of the distribution of galangal, the methods used to extract the active compounds of galangal, and the anticancer properties of both galangin and galangal. It is important to note that galangal and galangin primarily function by regulating the signaling pathways of PI3K/Akt, MAPK, AMPK, p53, NF-κB, and Ras/RAF/MEK/ERK, which in turn triggers apoptosis, autophagy, and ROS while preventing the migration and invasion of cancer cells. We also discussed their toxicity, bioavailability, and clinical uses. ConclusionIn conclusion, galangal extract and galangin have a lot of promise for treating cancer. It is anticipated that this review will further advance the use of galangal extract and galangin as potential cancer treatment medications. Moreover, the discovery and development of drugs based on galangal has enormous potential for the therapy of cancer.

Network Pharmacology Studies on the Molecular Mechanism of Hashimoto's Thyroiditis Treated with Shutiao Qiji Decoction.

In recent years, the number of patients with Hashimoto's thyroiditis has been increasing, and traditional Chinese medicine ingredients and combinations have been applied to treat Hashimoto's thyroiditis to increase efficacy and reduce side effects during the treatment process. Shutiao Qiji Decoction is one of the Chinese traditional medicine prescriptions, which is commonly used to treat cancer, tumor, etc. It is also used for thyroid-related diseases in the clinic. Hashimoto's thyroiditis is an autoimmune disease. In this study, the mechanism of Shutiao Qiji Decoction in treating Hashimoto's thyroiditis was studied through network pharmacology and molecular docking verification. Each Chinese medicine ingredient of Shutiao Qiji Decoction was retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The related genes of HT were searched from the UniProt and GeneCards databases. Meanwhile, we used Cytoscape to construct the protein-protein interaction (PPI) visual network analysis, and used the search tool to search the database of Interacting Genes (STRING) to build a PPI network. These key proteins were enriched and analyzed by molecular docking validation, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hashimoto's thyroiditis disease model was established in SD rats, and SQD was administered by gavage after the successful establishment of the model. After 6 weeks of continuous administration of the drug by gavage, tissue samples were collected and the thyroid and spleen tissues were visualized by HE staining to verify the therapeutic effect. The results showed that there were 287 TCM active ingredients, 1920 HT-related disease targets, and 176 drug and disease targets in SQD. Through PPI analysis, GP analysis, and KEGG analysis of the common targets of drugs and diseases, we found their pathways of action to be mainly cancer action pathway, PI3K-AKT signaling pathway, and T-cell action pathway. The active ingredients of the drugs in SQD, malvidin, stigmasterol, porin-5-en-3bta-ol, and chrysanthemum stigmasterol, were docked with the related target proteins, MAPK, GSK3β, TSHR, and NOTCH molecules. The best binding energies obtained from docking were mairin with TSHR, stigmasterol with TSHR, poriferast-5-en-3beta-ol with MAPK, and chryseriol with GSK3β, with binding energies of -6.84 kcal/mol, -6.53 kcal/mol, -5.03 kcal/mol, and -5.05 kcal/mol, respectively. HE staining sections of rat thyroid and spleen tissues showed that SQD had a therapeutic effect on Hashimoto's thyroiditis and restored its immune function. It is verified by molecular docking results that Shutiao Qiji Decoction has a potential therapeutic effect on Hashimoto's thyroiditis in the MAPK/TSHR/NOTCH signal pathway, and that the main components, mairin, stigmasterol, poriferast-5-en-3beta-ol, and chryseriol play a role in it. SQD has been shown to have a good therapeutic effect on Hashimoto's thyroiditis.

Efficacy of Tribulus terrestris on diabetes and sexual disorders: A narrative review

Tribulus terrestris L. (T. terrestris) is widely distributed worldwide (Australia, Europe, India, North Africa). It typically contains a substantial amount of active ingredients, especially saponins, alkaloids, flavonoids, tannins, terpenoids, and phenol carboxylic acids. Additionally, T. terrestris has been frequently used in folk medicine and as a food supplement, highlighting the importance of evaluating its phytopharmacological properties. Various hypotheses suggest that this species may have significant potential in preventing and improving various human conditions, including diabetes, inflammatory diseases, low sexual desire, and infertility. Phytochemical studies reveal a significant disparity in the content of active substances, with a notable gap in the concentrations of spirostanol saponins and furostanol, which are the predominant active ingredients associated with therapeutic effects. The objective of this present review is to evaluate T. terrestris -based formulations by exploring various potential mechanisms of action, aiming to determine whether the use of T. terrestris supplements is justified in the context of diabetes and its complications.

Experiments Validated the Development of Zebrafish Embryos and Toxicological Mechanism of Borneols in Perinatal Period.

Studies have confirmed that high dose borneol has perinatal toxicity and has a certain effect on embryonic development. However, there is little about the effect of borneol on the development of zebrafish embryos. Therefore, we compared the effects of D-borneol, L-borneol and synthetic borneol on the growth and development of zebrafish embryos, and predicted the possible mechanism of perinatal toxicity. The embryonic mortality rate, hatching rate, and heart rate of each group were recorded at 48 hpf to compare the effects of borneols on the development of zebrafish embryos. Network pharmacology and molecular docking technology were used to predict the possible mechanism of perinatal toxicity. We found that borneols increased the mortality at 24 and 48 hpf, inhibited the autonomous movement behavior at 24 hpf, and affected the hatching rate and heart rate at 48 hpf. Network pharmacology analysis showed that borneols had the same toxic targets in the perinatal period and were involved in regulating perinatal toxicity by regulating pathways in cancer, chemical carcinogenesis-receptor activation, PI3K-Akt and others. Molecular docking showed that the binding activity of the active ingredients and the core target was at a medium level, and the binding activity of the borneols active ingredients and the core target was not much different. Three kinds of borneol on the development of zebrafish embryos were different. The toxicity of L-borneol was the lowest. The mechanisms of perinatal toxicity were related to inflammation, apoptosis, cell cycle and growth, differentiation and reproduction.

Exploring Effects and Mechanism of Ingredients of Herba Epimedii on Osteogenesis and Osteoclastogenesis In Vitro.

Herba Epimedii, a commonly used traditional herb, has been proven effective in ameliorating osteoporosis. However, the active ingredients and potential mechanism need further exploration. To screen active ingredients of Herba Epimedii with the effect of ameliorating osteoporosis and to explore their potential mechanisms. TCMSP and Swiss Target Prediction were applied to collect the ingredients of Herba Epimedii and their targets. UniProt, GeneCards, TTD, DisGeNET, and OMIM were adopted to search osteoporosis-related genes. STRING and DAVID were used to perform enrichment analysis. Effects of screened ingredients were evaluated on MC3T3-E1 cells and RAW264.7 cells, respectively. Eleven ingredients were screened by Network Pharmacology. They exerted a promoting effect on MC3T3-E1 cells (10-9-10-5 M). The ingredients didn't significantly affect ALP activity and osteoblastogenesis-related genes. Baohuoside 1, Sagittatoside B, Chlorogenic acid, Cryptochlorogenic acid, and Neochlorogenic acid significantly increased calcium depositions. The ingredients didn't exhibit a dose-dependent inhibition or promotion on RAW264.7 cells. Baohuoside 1, Sagittatoside B, Neochlorogenic acid, Cryptochlorogenic acid, Icariin, Epimedin A, Chlorogenic acid, Sagittatoside A, and Epimedin C suppressed the level of TRACP. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, Sagittatoside A, and Icariin decreased the number of multinucleated osteoclastic cells. Baohuoside 1, Sagittatoside B, and Cryptochlorogenic acid could significantly inhibit MMP-9 expression. Neochlorogenic acid, Sagittatoside B, Chlorogenic acid, and Cryptochlorogenic acid promoted MC3T3-E1 differentiation, among which Neochlorogenic acid showed significant promotion in viability, mineralization, and OPN expression. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, and Icariin inhibited RAW264.7 differentiation, among which Baohuoside 1 showed significant inhibition on TRACP, multinucleated osteoclastic cells number and MPP-9 expression. The mechanism might relate to the FoxO signaling pathway, MAPK signaling pathway, and TNF signaling pathway.

Current View on How Human Gut Microbiota Mediate Metabolic and Pharmacological Activity of Panax ginseng. A Scoping Review.

Panax ginseng is one of the most important remedies in ancient Eastern medicine. In the modern Western world, its reputation started to grow towards the end of the XIX century, but the rather approximate understanding of action mechanisms did not provide sufficient information for an appropriate use. Nowadays, Panax ginseng is frequently used in some pathological conditions, but the comprehension of its potential beneficial effects is still incomplete. The purpose of this study is to highlight the most recent knowledge on mechanisms and effects of ginseng active ingredients on the intestinal microbiota. The human microbiota takes part in the immune and metabolic balance and serves as the most important regulator for the control of local pathogens. This delicate role requires a complex interaction and reflects the interconnection with the brainand the liver-axes. Thus, by exerting their beneficial effects through the intestinal microbiota, the active ingredients of Panax ginseng (glycosides and their metabolites) might help to ameliorate both specific intestinal conditions as well as the whole organism's homeostasis.

Unifying Theory and Experiments: Multi-Target Pharmacology of Dajihan Pill Against Hyperlipidemia

Background: The increasing incidence of hyperlipidemia (HLP) is attributed to the imbalance in redox homeostasis, aberrant lipid metabolism, and the excessive intake of empty calories. Dajihan Pill (DJHP) is a Traditional Chinese Medicine (TCM) formula composed of Zingiberis Rhizoma (ZR), Piperis Longi Fructus (PLF), Alpiniae Officinarum Rhizome (AOR), and Cinnamomi Cortex (CC) in a ratio of 3:2:3:2. It exhibits a significant preventive effect on HLP. Certainly, the active components and the precise mechanism of action are not fully understood. Therefore, this study aims to elucidate the preventive and ameliorative mechanisms of DJHP against HLP by integrating network pharmacology, molecular docking, and experimental validation. Methods: Based on the pharmacological method, active ingredients in DJHP and targets were extracted from Traditional Chinese Medicine System Pharmacology (TCMSP) and UniProt. Then core compounds and targets were obtained by constructing “compounds-targets-disease” and proteinprotein interaction (PPI) network. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to elucidate further the associated action mechanism. The molecular binding mechanisms between the core ingredients and targets were elucidated through molecular docking. Additionally, the antioxidant capacities of DJHP extracts were investigated by assessing their DPPH, hydroxyl, and ABTS radical scavenging activities. Results: A total of 45 active compounds and 258 targets were identified in DJHP. Network analysis indicated that quercetin, beta-sitosterol, kaempferol, and oleic acid might serve as core bioactive compounds. Seven core targets, including AKT1, INS, and TNF, were identified as potential preventive targets. GO analysis suggested the improvement of HLP by DJHP may be related to the lipid metabolic process, high-density lipoprotein particle, triglyceride binding, and inflammatory response. The KEGG analysis indicated TNF, HIF-1, and AMPK signaling pathways were involved. The observations of active compounds binding with core targets indicated an excellent combination. Additionally, antioxidant results showed that DJHP exhibited significant DPPH, hydroxyl, and ABTS radical scavenging activities. Conclusion: Theoretical and experimental investigations indicate that DJHP can effectively modulate various signaling pathways and enhance the redox system, thus mitigating HLP. Our work provided a basis for the pharmacological study of DJHP in preventing HLP and further research.

The Impact of Carrageenan on Pharmascience

Abstract: Carrageenan (CG) a sulfated polysaccharide (SP) is produced using a variety of seaweeds from the Rhodophyceae family. This type of seaweed is available in areas, like the Atlantic Ocean close to Great Britain, Europe, and North America. Carrageenan has been permitted for the use as food items with the European additive E-number E407. Carrageenan is a widely used polysaccharide derived from red seaweed and is known for its various applications in the chemical, biological, and pharmaceutical fields. It delves into its versatile applications across various sub areas, spanning from the food to the pharmaceutical industry. A significant emphasis is placed on the intricate roles of carrageenan in pharmaceutical science, where it serves as both a drug carrier agent and an active ingredient, owing to its noteworthy biological activity. This review aims to provide a comprehensive overview of carrageenan's versatile applications, with a focus on its chemical properties, biological activities, and pharmaceutical uses. The pharmaceutical applications of carrageenan are further categorized into various subparts, including its role in treating diseases and its use in drug delivery systems, such as topical, oral, nasal, and unconventional routes. The review also incorporates the most recent developments in clinical trials involving carrageenan and its updated applications, drawing from authoritative sources. This comprehensive analysis aims to offer readers a clear understanding of carrageenan's multifaceted nature and its evolving significance in diverse industries.

Targets and Mechanisms of Xuebijing in the Treatment of Acute Kidney Injury Associated with Sepsis: A Network Pharmacology-based Study.

Sepsis is a state of the systemic inflammatory response of the host induced by infection, frequently affecting numerous organs and producing varied degrees of damage. The most typical consequence of sepsis is sepsis-associated acute kidney injury(SA-AKI). Xuebijing is developed based on XueFuZhuYu Decoction. Five Chinese herbal extracts, including Carthami Flos, Radix Paeoniae Rubra, Chuanxiong Rhizoma, Radix Salviae, and Angelicae Sinensis Radix, make up the majority of the mixture. It has properties that are anti-inflammatory and anti-oxidative stress. Xuebijing is an effective medication for the treatment of SA-AKI, according to clinical research. But its pharmacological mechanism is still not completely understood. First, the composition and target information of Carthami Flos, Radix Paeoniae Rubra, Chuanxiong Rhizoma, Radix Salviae, and Angelicae Sinensis Radix were collected from the TCMSP database, while the therapeutic targets of SA-AKI were exported from the gene card database. To do a GO and KEGG enrichment analysis, we first screened the key targets using a Venn diagram and Cytoscape 3.9.1. To assess the binding activity between the active component and the target, we lastly used molecular docking. For Xuebijing, a total of 59 active components and 267 corresponding targets were discovered, while for SA-AKI, a total of 1,276 targets were connected. There were 117 targets in all that was shared by goals for active ingredients and objectives for diseases. The TNF signaling pathway and the AGE-RAGE pathway were later found to be significant pathways for the therapeutic effects of Xuebijing by GO analysis and KEGG pathway analysis. Quercetin, luteolin, and kaempferol were shown to target and modulate CXCL8, CASP3, and TNF, respectively, according to molecular docking results. This study predicts the mechanism of action of the active ingredients of Xuebijing in the treatment of SA-AKI, which provides a basis for future applications of Xuebijing and studies targeting the mechanism.

Variations in volatile components and biological activities of essential oils from Citrus aurantium ‘changshanhuyou’ at different growth and ripening stages

Citrus aurantium ’Changshanhuyou’ is one kind of fruit that is beneficial to human health. Most research focus on active substances such as flavonoids and limonoids, but few on the essential oils from its peels. This study analyzed the volatile components of Huyou peel essential oil (HYEO) throughout the growth and ripening stages including beginning, middle, end of growth period, and post- ripening stage (60 days of storage) by GC–MS. The results identified approximately 70 components in HYEO, and the level of oxygenated monoterpenes decreased while sesquiterpenes increased with the ripening of the huyou. The essential oil after 60 days of storage showed outstanding antioxidant properties (DPPH, IC50 = 101.77 ± 0.83 mg/mL; ABTS, IC50 = 18.11 ± 0.74 mg/mL), antibacterial (zones of inhibition: E. coli, 28.18 ± 1.37 mm; S. aureus, 20.40 ± 0.84 mm; S. Typhimurium, 27.17 ± 1.14 mm; L. monocytogenes, 22.83 ± 1.27 mm) and antidiabetic (IC50 = 5.26 ± 0.58 mg/mL) activities due to high levels of p-cymenene, cis-carveol, and D-carvone detected. Results from the corticosterone-damaged mouse neuronal cell model, the essential oil extracted from the middle of the growth period demonstrates the best antidepressant activity due to high content of citronellol, elemene, linalool, and citronel detected. Overall, this study provides a valuable reference for exploiting and evaluating essential oils from Huyou peels with multifunctions in food and medicine industry.

Isolation, purification and comparison of soluble active substances from four peony roots

Due to high medicinal and economic value of Paeonia L., roots from 4-year-old, 5-year-old, and 6-year-old Paeonia ostii (4PO, 5PO, 6PO), as well as medicinal Paeonia suffruticosa (PS), Paeonia lactiflora (PL) and Paeonia vetchii Lynch (PV) were utilized to isolate and purify soluble activity substances. Through static and dynamic experiments, it was established that LX-83 macroporous resin effectively purified the crude extract of peony root (PR) under optimal conditions: Absorption to the column at 2 BV/h for 6 h, followed by desorption with 60 % ethanol at 5 BV/h for 0.8 h. After purification, the average total phenolic content of six PR crude extracts surged from 147.8 mg GAE/g dry weight (dw) to 397.5 mg GAE/g dw. Eight terpenes, 13 phenols, 6 flavonoids, and 4 tannins in crude PR extracts were identified by HPLC-MS. The content of paeoniflorin, pentagalloylglucose, mudanpioside C, benzoyloxidized paeoniflorin, benzoyl paeoniflorin, and paeonol was determined by HPLC, which increased by 3–5.2 times. The purified PO and PS extracts contain significantly abundant amounts of paeonol and paeoniflorin, exceeding the standards of 1.2 % and 1.6 % in the Chinese Pharmacopoeia, respectively. Moreover, the purified PR extracts exhibited enhanced antioxidant activity and anti-tyrosinase activity, with 5PO and 6PO extracts demonstrating the highest efficacy. This study successfully developed a versatile and effective method for purifying active substances in various PRs. It also provided theoretical and practical insights for upgrading and transforming the root industry of Paeonia plants.

The Synergistic Effect of Curcumin and Piperine Nanoparticles on Methamphetamine-induced Neurotoxicity, Oxidative Stress, and Memory Impairments in Mice Brain

Background: Methamphetamine (METH) is a highly addictive neural stimulant that severely affects the CNS and can induce oxidative damage. Piperine and curcumin are active constituents that have numerous properties, including antioxidant, anti-inflammatory, and neuroprotective Objective: In this study, the synergistic effect of piperine and curcumin nanoparticles was investigated on the acute doses of METH-induced neurotoxicity in mice brains. Methods: METH (6 mg/kg, i.p) was administered to 14 groups of mice and piperine-curcumin nanoparticles at different doses (10, 20, 40 mg/kg and 20, 40 and 60 mg/kg, respectively) were administered. Open field test (OFT) and conditioned place preference (CPP) were used to investigate locomotor activity, anxiety-like behavior, and addictive behavior in mice. Oxidative stress biomarkers (reactive oxygen species (ROS), protein carbonyl content, lipid peroxidation, glutathione content, and mitochondrial function were evaluated in isolated brain mitochondria. Results: We found that piperine and curcumin nanoparticles significantly decreased hyperlocomotion and anxiety-like behavior in METH-treated mice. Also, METH enhanced CPP whilst piperine and curcumin nanoparticles suppressed the effect of METH-induced CPP. METH administration significantly increased ROS, protein carbonyl content, and lipid peroxidation and decreased glutathione content and mitochondrial function in the isolated brain mitochondria. Piperine and curcumin nanoparticles (at all doses) showed synergistic effects on reducing oxidative damages in a dosedependent manner compared to the METH group. Conclusion: In conclusion, combined piperine and curcumin nanoparticles showed greater neuroprotective effects against METH-induced neurotoxicity due to their greater permeability and better antioxidant properties than piperine and curcumin alone

Cubosomes hydrogel containing silver based organometallic compounds for enhanced wound healing of burns: In vitro and in vivo studies

The aim of this study is to investigate the treatment of burn wounds and bacterial infections, specifically focusing on silver(I) N-heterocyclic carbene (Ag-NHC) loaded into cubosomes. Ag-NHC is an organometallic complex of silver (Ag) and can be considered an active pharmaceutical ingredient for the topical treatment of burns. A novel nanoparticle system, cubosome dispersions, was formulated using high pressure homogenization methods with different concentrations of lipid phase glyceryl monooleate (GMO), surfactants such as poloxamer 407 (F-127), and polyvinyl alcohol (PVA). The optimized formulation (U6) was characterized by in vitro drug release profile (90.54 ± 1.17 %), particle size (126.7 ± 0.98 nm), zeta potential (−21.6 ± 6.83 mV), entrapment efficiency (89.30 ± 1.46 %), and morphology as observed by transmission electron microscopy (TEM). The U6 formulation was incorporated into a hydrogel containing Carbopol 940 to form a cubosomal hydrogel (cubogel). The cubogel was characterized by the in vitro release of Ag-NHC (92 %), entrapment efficiency (>90 %), pH (5.3), viscosity (1.2 cP), spreadability, and TEM. From the in vitro drug release pattern, it was concluded that the U6 formulation showed slow and sustained drug release over 24 h, and demonstrated superior burn healing compared to marketed products. The in vivo wound healing study revealed that the cubogel demonstrated a superior burn healing rate compared to commercially available products (Quench® and Clotrimazole®). The in vivo histopathological results showed that the prepared cubogel was effective in treating second-degree burns, with no side effects or skin irritation, compared to commercial products. Additionally, Ag-NHC-loaded cubogel facilitated sustained release for treating burn wounds without any bacterial infections. The current findings provide a strong basis for the initiating phase 0 clinal trials, highlighting significant potential for the further research to benefit the pharmaceutical industry.

Self-delivered sonodynamic nanomedicine for enhanced tumor immunotherapy by simultaneously reversing the immunosuppression and immune resistance

Sonodynamic therapy (SDT) shows potential for noninvasive eradication of local solid tumors. However, its efficacy in suppressing metastatic tumors is limited by factors such as insufficient tumor accumulation, the immunosuppressive tumor microenvironment, and acquired immune tolerance. To address these challenges, we developed self-delivering sonodynamic nanomedicine incorporating Toll-like receptor (TLR) agonists R848 and programmed death-ligand 1 (PD-L1) inhibitors JQ1 for combined SDT and immunotherapy. These nanomedicines enhanced tumor accumulation of sonosensitizers, enabling potent SDT and induction of immunogenic cell death (ICD). Additionally, the co-encapsulated R848 and JQ1 alleviated tumor immunosuppression and immune tolerance, synergizing effectively with SDT to elicit a robust antitumor immune response. By integrating enhanced SDT with activated antitumor immunity, significant inhibition of primary, distant, and lung metastatic tumors was achieved. This study introduces a novel approach for combining SDT with immunotherapy using self-assembled active pharmaceutical ingredients.