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Physiologically based pharmacokinetic/toxicokinetic (PBPK/PBTK) models are designed to elucidate the mechanism of chemical compound action in organisms based on the physiological, biochemical, anatomical, and thermodynamic properties of organisms. After nearly a century of research and practice, good results have been achieved in the fields of medicine, environmental science, and ecology. However, there is currently a lack of a more systematic review of progress in the main research directions of PBPK models, especially a more comprehensive understanding of the application in aquatic environmental research. In this review, a total of 3974 articles related to PBPK models from 1996 to 24 March 2024 were collected. Then, the main research areas of the PBPK model were categorized based on the keyword co-occurrence maps and cluster maps obtained by CiteSpace. The results showed that research related to medicine is the main application area of PBPK. Four major research directions included in the medical field were "drug assessment", "cross-species prediction", "drug–drug interactions", and "pediatrics and pregnancy drug development", in which "drug assessment" accounted for 55% of the total publication volume. In addition, bibliometric analyses indicated a rapid growth trend in the application in the field of environmental research, especially in predicting the residual levels in organisms and revealing the relationship between internal and external exposure. Despite facing the limitation of insufficient species-specific parameters, the PBPK model is still an effective tool for improving the understanding of chemical–biological effectiveness and will provide a theoretical basis for accurately assessing potential risks to ecosystems and human health. The combination with the quantitative structure–activity relationship model, Bayesian method, and machine learning technology are potential solutions to the previous research gaps. [ABSTRACT FROM AUTHOR]

Poultry may face simultaneous exposure to aflatoxin B1 (AFB1) and tiamulin (TIA), given mycotoxin contamination and antibiotic use. As both mycotoxins and antibiotics can affect cytochrome P450 enzymes (CYP450), our study aimed to explore their interaction. We developed UHPLC-MS/MS methods for the first-time determination of the interaction between TIA and AFB1 in vitro and in vivo in broiler chickens. The inhibition assay showed the half maximal inhibitory concentration (IC50) values of AFB1 and TIA in chicken liver microsomes are more than 7.6 μM, indicating an extremely weak inhibitory effect on hepatic enzymes. Nevertheless, the oral TIA pharmacokinetic results indicated that AFB1 significantly increased the area under the plasma concentration-time curve (AUClast) of TIA by 167% (p < 0.01). Additionally, the oral AFB1 pharmacokinetics revealed that TIA increased the AUClast and mean residence time (MRT) of AFB1 by 194% (p < 0.01) and 136%, respectively. These results suggested that the observed inhibition may be influenced by other factors, such as transport. Therefore, it is meaningful to further explore transport and other enzymes, involved in the interaction between AFB1 and TIA. Furthermore, additional clinical studies are necessary to thoroughly assess the safety of co-exposure with mycotoxins and antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anticolorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited preclinical evidence and safety concerns. This study aimed to determine the preclinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration. Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS. Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p < 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 μg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 μg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair. Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration.c [ABSTRACT FROM AUTHOR]

The cefquinome samples from plasma were extracted and separated by HPLC on a reversed phase C-18 column with mobile phase of acetonitrile and formic acid (0.1%) solution-(90:10, v/v). The calibration curves were linear ranged from 0.01-5μg/mL. The limit of quantification (LOQ) and limit of detection (LOD) were 0.04 and 0.01 μg/mL. The recovery of cefquinome from plasma was 73.4%, 78.33%, and 77% for low, medium and high concentration samples. The intraday and inter day relative standard deviation were less than 15%. The Cefquinome were found to be stable for more than 3 month at -70oC (degree symbol) and more than 24 h at 4oC. The present method has been applied successfully for the pharmacokinetics study in cattle. After intramuscular administration, the mean peak serum Concentrations (Cmax) was found 2.95μg/mL and achieved after (Tmax) 1.50h. The elimination half-life (tl/2(el)) was 2.03±0.06h. The Mean Residence Time (MRT) was 2.58±0.05h and the area under curve from zero time to infinity (AUC0-μž) were 9.67±0.72μg/mL/h. The newly proposed method was shown to be simple, rapid, economical and sensitive compared to the previously reported method, and thereafter applicable for the pharmacokinetics study in animals. [ABSTRACT FROM AUTHOR]

GuHong injection is composed of safflower and N-acetyl-L-glutamine. It is widely used in clinical for cerebrovascular diseases, such as ischemic stroke and related diseases. The objective of this review is to comprehensively summarize the most recent information related to GuHong in the treatment of stroke, including chemical composition, clinical studies, potential pharmacological mechanisms and pharmacokinetics. Additionally, it examines possible scientific gaps in current study and aims to provide a reliable reference for future GuHong studies. The systematic review reveals that the chemical composition of safflower in GuHong is more than 300 chemical components in five categories. GuHong injection is primarily used in clinical applications for acute ischemic stroke and related diseases. Pharmacological investigations have indicated that GuHong acts in the early and recovery stages of ischemic stroke by anti-inflammatory, anti-oxidative stress, anti-coagulation, neuroprotective and anti-apoptotic mechanisms simultaneously. Pharmacokinetic studies found that the main exposed substances in rat plasma after GuHong administration are hydroxysafflor yellow A and N-acetyl-L-glutamine, and N-acetyl-L-glutamine could exert its pharmacological effect across the blood-brain barrier. As a combination of Chinese herb and chemical drug, GuHong injection has great value in drug research and clinical treatment, especially for ischemic stroke disease. This article represents a comprehensive and systematic review of existing studies on GuHong injection, including chemical composition, pharmacological mechanism, and pharmacokinetics, which provides reference significance for the clinical treatment of ischemic stroke with GuHong, as well as provides guidance for further study. [ABSTRACT FROM AUTHOR]

Because of the high research and development cost of new drugs, the long development process of new drugs, and the high failure rate at later stages, combining past drugs has gradually become a more economical and attractive alternative. However, the ensuing problem of drug–drug interactions (DDIs) urgently need to be solved, and combination has attracted a lot of attention from pharmaceutical researchers. At present, DDI is often evaluated and investigated from two perspectives: pharmacodynamics and pharmacokinetics. However, in some special cases, DDI cannot be accurately evaluated from a single perspective. Therefore, this review describes and compares the current DDI evaluation methods based on two aspects: pharmacokinetic interaction and pharmacodynamic interaction. The methods summarized in this paper mainly include probe drug cocktail methods, liver microsome and hepatocyte models, static models, physiologically based pharmacokinetic models, machine learning models, in vivo comparative efficacy studies, and in vitro static and dynamic tests. This review aims to serve as a useful guide for interested researchers to promote more scientific accuracy and clinical practical use of DDI studies. [ABSTRACT FROM AUTHOR]

A class of drugs known as calcium channel blockers (CCBs) is used to treat hypertension, angina, and arrhythmias. There are two subcategories of this medication class: dihydropyridines and non-dihydropyridines. Studies on CYP3A5*3, AGTR1 rs275653, ABCB1 (MDR1) rs1045642, and POR*28 A503V have all investigated the effects of SNPs on CCBs. In this study, further research will be conducted to determine which SNPs most influence the efficacy of CCBs. The narrative reviews in this article come from a variety of sources. We performed searches in Pubmed, ScienceDirect, and Google Scholar using the terms "calcium channel blocker," "efficacy," "blood pressure response," "pharmacokinetic," and "polymorphism" OR "genetic" OR "genomic" to find relevant articles. When prescribing antihypertensive drugs, especially calcium channel blockers, it is essential to consider specific gene variants, for example, CYP3A5*3/*3, CYP3A4 *1G/*1G, MDR1 C3435T, RyR3 gene rs877087, because of their significant effects. [ABSTRACT FROM AUTHOR]

Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies. [ABSTRACT FROM AUTHOR]

The current study aimed to explore the pharmacokinetics of danofloxacin in non‐laying hens after a single oral (PO) and intravenous (IV) dose, both at 5 mg/kg body weight (BW). Eighteen 13‐week‐old healthy hens were equally and randomly divided into two groups. After both doses, blood samples (approximately 1 ml) were collected at different time points. Danofloxacin concentrations were quantified by a validated high‐performance liquid chromatography (HPLC) method followed by a non‐compartmental analysis using the software of WinNonLin. The elimination half‐lives (t1/2λzs) after PO and IV routes were determined as 8.15 ± 3.37 and 7.69 ± 3.40 h, respectively. After IV administration, danofloxacin had an initial concentration (C0) of 3.62 μg/ml, a volume of distribution at steady state (VSS) of 3579.72 ± 454.29 ml/kg, and a total body clearance (Cl) of 0.49 ml/h/g. After PO administration, the absolute bioavailability and absorption half‐life (t1/2ka) were calculated as 100.99% ± 23.10% and 0.82 ± 0.58 h, respectively. Based on the calculated ratio values of AUC/MIC and Cmax/MIC, an oral dose of 5 mg/kg danofloxacin would be expected to successfully treat hens infected with strains with MIC values ≤0.1 μg/ml. [ABSTRACT FROM AUTHOR]

Monotropein, a principal natural compound in iridoid glycosides extracted from Morindae officinalis radix, has potent pharmacological activities. To understand and utilize monotropein, we systematically summarized the studies on monotropein, including its biosynthetic pathway, physicochemical properties, pharmacokinetics, and pharmacology. Interestingly, we found that the multiple bioactivities of monotropein, such as anti-osteoporosis, anti-inflammation, antioxidation, anti-nociception, and hepatic or renal protection, are closely associated with its capability of downregulating the nuclear factor-B signaling pathway, inhibiting the mitogen-activated protein kinase signaling pathway, attenuating the activation of nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway, and regulating the mammalian target of rapamycin/autophagy signaling pathway. However, the clinically therapeutic effects and the potential problems need to be addressed. This review highlights the current research progress on monotropein, which provides a reference for further investigation of monotropein. [ABSTRACT FROM AUTHOR]

Atractylodes lancea (Thunb.) DC. (A. lancea: AL) is a promising candidate for the treatment of cholangiocarcinoma (bile duct cancer). The study investigated (i) the propensity of capsule formulation of the standardized extract of AL (formulated AL) to modulate mRNA and protein expression and activities of CYP1A2 and CYP3A1 in rats after long- and short-term exposure, (ii) the pharmacokinetics of atractylodin (ATD: active constituent) after long-term administration of formulated AL, and (iii) the biodistribution of atractylodin-loaded polylactic-co-glycolic acid (ATD-PLGA-NPs) in mice. To investigate CYP1A2 and CYP3A1 modulatory activities following long-term exposure, rats of both genders received oral doses of the formulated AL at 1,000 (low dose), 3,000 (medium dose), and 5,000 (high dose) mg/kg body weight daily for 12 months. For short-term effects, male rats were orally administered the formulated AL at the dose of 5,000 mg/kg body weight daily for 1, 7, 14 and 21 days. The pharmacokinetic study was conducted in male rats after administration of the formulated AL at the dose of 5,000 mg/kg body weight daily for 9 months. The biodistribution study was conducted in a male mouse receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg body weight. The high dose of formulated AL produced an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 activities in male rats. The low dose, however, did not inhibit or induce the activities of both enzymes in male and female rats. ATD reached maximum plasma concentration (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence time (MRT) and terminal phase elimination half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in mouse livers receiving ATD-PLGA-NPs was 5-fold of that receiving free ATD. Clinical use of low-dose AL should be considered to avoid potential herb-drug interactions after long-term use. ATD-PLGA-NPs is a potential drug delivery system for cholangiocarcinoma treatment. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) infection and the associated acquired immune deficiency syndrome (AIDS) remain global challenges even after decades of successful treatment, with eastern and southern Africa still bearing the highest burden of disease. Following a thorough computational study, we report top 10 phytochemicals isolated from Croton dichogamus as potent reverse transcriptase inhibitors. The pentacyclic triterpenoid, aleuritolic acid (L12) has displayed best docking pose with binding energy of -8.48 kcal/mol and Ki of 0.61 μM making it superior in binding efficiency when compared to all docked compounds including the FDA-approved drugs. Other phytochemicals such as crotoxide A, crothalimene A, crotodichogamoin B and crotonolide E have also displayed strong binding energies. These compounds could further be investigated as potential antiretroviral medication. [ABSTRACT FROM AUTHOR]

Background: Numerous drugs have the potential to be affected by cytochrome P450 (CYP) 2B6-mediated drug-drug interactions (DDIs).Objectives: In this work, we extend a static approach to the prediction of the extent of pharmacokinetics DDIs between substrates and inhibitors or inducers of CYP2B6.Methods: This approach is based on the calculation of two parameters (the contribution ratio [CR], representing the fraction of dose of the substrate metabolized via this pathway and the inhibitory or inducing potency of the perpetrator [IR or IC, respectively]) calculated from the area under the concentration-time curve (AUC) ratios obtained in in-vivo DDI studies.Results: Forty-eight studies involving 5 substrates, 11 inhibitors and 18 inducers of CYP2B6 (overall 15 inhibition and 33 induction studies) were divided into test and validation sets and considered for estimation of the parameters. The proposed approach demonstrated a fair accuracy for predicting the extent of DDI related to CYP2B6 inhibition and induction, all predictions related to the validation test (N = 18) being 50-200% of the observed ratios.Conclusions: This methodology can be used for proposing initial dose adaptations to be adopted, for example in clinical use or for designing DDI studies involving this enzyme. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) are usually treated as multifunctional agents combining several therapeutical applications, like imaging and targeting delivery. However, clinical translation is still largely hindered by several factors, and the rapidly formed protein corona on the surface of NPs is one of them. The formation of protein corona is complicated and irreversible in the biological environment, and protein corona will redefine the "biological identity" of NPs, which will alter the following biological events and therapeutic efficacy. Current understanding of protein corona is still limited and incomplete, and in many cases, protein corona has adverse impacts on nanomedicine, for instance, losing targeting ability, activating the immune response, and rapid clearance. Due to the considerable role of protein corona in NPs' biological fate, harnessing protein corona to achieve some therapeutic effects through various methods like biomimetic approaches is now treated as a promising way to meet the current challenges in nanomedicine such as poor pharmacokinetic properties, off-target effect, and immunogenicity. This review will first introduce the current understanding of protein corona and summarize the investigation process and technologies. Second, the strategies of harnessing protein corona with biomimetic approaches for nanomedicine design are reviewed. Finally, we discuss the challenges and future outlooks of biomimetic approaches to tune protein corona in nanomedicine. [ABSTRACT FROM AUTHOR]

Cortex fraxini is a widely used traditional Chinese medicine. Esculin is one of the main active ingredients of Cortex fraxini and has attracted more and more attention from scholars. The purpose of the review is to systematically review relevant studies on the pharmacological effects and pharmacokinetic characteristics of esculin to support its further application as therapeutic agents. Pharmacological studies have shown that the anti‐inflammatory and anti‐oxidative stress effects of esculin are outstanding. This indicates that esculin is promising to be used to treat a variety of diseases closely related to inflammation and oxidative damage. Esculin has anti‐diabetic effect, which is closely related to improving pancreas damage, promoting insulin release, and enhancing glucose homeostasis. In addition, esculin has anti‐cancer, antibiosis, anti‐virus, neuroprotection, anti‐thrombosis and treating eye diseases properties. Pharmacokinetic studies show that esculin can be quickly and evenly distributed in the body. However, the first pass effect of esculin is serious. In short, esculin is promising to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of esculin. [ABSTRACT FROM AUTHOR]

The impact of probiotics on difloxacin disposition in Mycoplasma gallisepticum-infected chickens after intravenous and oral administration (10 mg/kg) and its tissue residues after oral administration (10 mg/kg for 5 days) was studied. Difloxacin concentrations were estimated by the high-performance liquid chromatography method. Following intravenous administration of difloxacin, the volume of distribution in probiotic-pretreated Mycoplasma gallisepticum-infected chickens (4.05 ± 0.07) was less than that in non-treated birds (4.16 ± 0.07 mg/µg/mL). The t1/2β of difloxacin in probiotic-pretreated Mycoplasma gallisepticum-infected chickens (4.75 ± 0.09 hours) was significantly longer than that in the non-treated ones (4.55 ± 0.05 hours). The total body clearance of the drug from the plasma of probiotic-pretreated Mycoplasma gallisepticum-infected chickens (0.64 ± 0.00 mg/(µg/mL)/h) was less than that in non-treated ones (0.69 ± 0.01 mg/(µg/mL)/h). The area under the curve extrapolated to last plasma concentration0-t (15.20 ± 0.08 µg/mL/h) and the mean residence time (6.33 ± 0.11 hours) values in probiotic-pretreated Mycoplasma gallisepticum-infected chickens were larger than those in non-treated ones (14.13 ± 0.22 ig/mL/h and 6.02 ± 0.06 hours). The drug was rapidly absorbed orally in probiotic-pretreated Mycoplasma gallisepticum-infected chickens compared to non-treated ones (t1/2ab 1.47 ± 0.02 vs. 1.53 ± 0.05 hours). The peak serum concentration of difloxacin in probiotic-pretreated Mycoplasma gallisepticum-infected chickens was higher than that in non-treated ones (1.46 ± 0.07 vs. 1.18 ± 0.07 µg/mL) and was achieved at shorter time to peak concentration (2.59 ± 0.01 vs. 2.74 ± 0.05 hours). Residue levels of difloxacin were lower in probiotic-pretreated Mycoplasma gallisepticum-infected chickens than in non-treated ones in all examined tissues. [ABSTRACT FROM AUTHOR]

Background. Azithromycin (AZM) is one of the most common broad-spectrum antibiotics. However, drug resistance is increasing and combination therapy has attracted great attention. AZM is usually combined with traditional Chinese medicine (TCM) preparations with heat-clearing and detoxifying effects, including Kumu injection (KM) made from Picrasma quassioides (D. Don) Benn. Purpose. The present study aimed to investigate synergistic antimicrobial and anti-inflammatory activities of KM plus AZM with the aim of understanding the mechanism of clinical efficacy of combination regimens. Methods. Seven common bacterial clinical isolates and LPS-induced RAW 264.7 cells were used for assay of in vitro potency. The minimum inhibitory concentration (MIC) was determined for each drug, followed by synergy testing through the checkerboard method and fractional inhibitory concentration index (FICI) for quantifying combined antibacterial effects. The rat model of Klebsiella pneumoniae-induced pneumonia was developed and subjected to various drug treatments, namely, AZM, KM, or AZM plus KM, intravenously administered at 75 mg/kg once a day for one week. The combination effects then were evaluated according to pharmacodynamics and pharmacokinetic assessments. Results. KM-AZM combination synergistically inhibits in vitro growth of all the test standard strains except Pseudomonas aeruginosa and also the drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Shigella dysenteriae, Klebsiella pneumoniae, and Escherichia coli. Despite an additive effect against NO, KM plus AZM at an equal dose could synergistically suppress overrelease of the inflammatory cytokines TNF-α and IL-6 by LPS-induced RAW 264.7 cells. The combination significantly inhibited the proliferation of K. pneumoniae in the rat lungs, mainly by inactivating MAPKs and NF-κB signaling pathways. KM-AZM combination caused a onefold increase in apparent distribution volume of AZM, along with a significant decrease of AZM level in the livers and heart for pharmacokinetics. Conclusion. KM-AZM combination displayed synergistic antibacterial and anti-inflammatory effects beneficial to the therapeutic potential against bacterial infection. [ABSTRACT FROM AUTHOR]

As a fluoroquinolone antimicrobial agent, danofloxacin is mainly used to treat avian bacterial and mycoplasma infections. The pharmacokinetic characteristics of danofloxacin are usually explored in healthy animals, while those in endotoxemic broilers are still rare. This study aimed to investigate the pharmacokinetics of danofloxacin in endotoxemic broilers induced by Escherichia coli (E. coli) lipopolysaccharide (LPS) after single oral administration. Ten healthy 5‐week‐old Arbor Acres (AA) broilers with similar body weight (BW) were randomly and equally divided into LPS and control groups. The LPS group was intravenously injected with an LPS of E. coli O55: B5 at 2.5 mg/kg BW, and the control group was intravenously injected with the same volume of sterile saline. Danofloxacin was administered orally at a dose of 5 mg/kg BW immediately 1 h after the intravenous injection of LPS or sterile saline. Rectal temperature was measured at predetermined times points in all broilers, and plasma and serum samples were taken. The interleukin‐6 (IL‐6) levels in serum samples were detected by the enzyme‐linked immunosorbent assay (ELISA) kits, and danofloxacin concentrations in plasma were detected through the high‐performance liquid chromatography (HPLC) method and subjected to a compartmental analysis using Phoenix software. The LPS challenge led to biphasic adaptive changes in broiler body temperature and increased the levels of IL‐6. Compared with the control group, LPS treatment significantly prolonged the time to the peak concentration (LPS: 8.75 ± 3.88 h; Control: 3.20 ± 2.20 h). However, there were no significant differences in the other pharmacokinetic parameters between both groups. [ABSTRACT FROM AUTHOR]

Pogostemonis Herba (PH) is the dried aerial parts of Pogostemon cablin (Blanco) Benth, which is mainly distributed and used in Asian countries. PH is an aromatic damp-resolving drug in traditional Chinese medicine (TCM), which is usually used for the treatment of vomiting, chest tension, tiredness, abdominal pain, diarrhea, and headache. In this review, the summary of chemical constituents in the aerial parts, biological activities, history of uses, quality control methods, industrial applications, pharmacokinetics and network pharmacology are reported. By collating the chemical constituents of various parts of PH, a total of 174 components were identified, including 66 terpenes, 6 pyrones, 40 flavonoids, 21 phenylpropanoids, 9 steroids, 4 polysaccharides and 28 others. Pharmacological research has found that PH possesses multi-pharmacological activities, including regulating the gastrointestinal tract, inhibition of pathogenic microorganisms, and anti-inflammation, which provide more scientific interpretation for the clinical usage of PH. In addition, the shortcomings of the current research on PH and the recommendation of future studies on PH are analyzed. We hope this review can provide some insight for further research and applications of PH in future. [ABSTRACT FROM AUTHOR]

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin. [ABSTRACT FROM AUTHOR]

Andrographis paniculata (Burm. f.) Wall. ex Nees, a renowned herb medicine in China, is broadly utilized in traditional Chinese medicine (TCM) for the treatment of cold and fever, sore throat, sore tongue, snake bite with its excellent functions of clearing heat and toxin, cooling blood and detumescence from times immemorial. Modern pharmacological research corroborates that andrographolide, the major ingredient in this traditional herb, is the fundamental material basis for its efficacy. As the main component of Andrographis paniculata (Burm. f.) Wall. ex Nees, andrographolide reveals numerous therapeutic actions, such as antiinflammatory, antioxidant, anticancer, antimicrobial, antihyperglycemic and so on. However, there are scarcely systematic summaries on the specific mechanism of disease treatment and pharmacokinetics. Moreover, it is also found that it possesses easily ignored security issues in clinical application, such as nephrotoxicity and reproductive toxicity. Thereby it should be kept a lookout over in clinical. Besides, the relationship between the efficacy and security issues of andrographolide should be investigated and evaluated scientifically. In this review, special emphasis is given to andrographolide, a multifunctional natural terpenoids, including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches. A brief overview of its clinical trials is also presented. This review intends to systematically and comprehensively summarize the current researches of andrographolide, which is of great significance for the development of andrographolide clinical products. Noteworthy, those un‐cracked issues such as specific pharmacological mechanisms, security issues, as well as the bottleneck in clinical transformation, which detailed exploration and excavation are still not to be ignored before achieving integration into clinical practice. In addition, given that current extensive clinical data do not have sufficient rigor and documented details, more high‐quality investigations in this field are needed to validate the efficacy and/or safety of many herbal products. [ABSTRACT FROM AUTHOR]

Machine learning (ML), as a branch of artificial intelligence, acquires the potential and meaningful rules from the mass of data via diverse algorithms. Owing to all research of traditional Chinese medicine (TCM) belonging to the digitalization of clinical records or experimental works, a massive and complex amount of data has become an inextricable part of the related studies. It is thus not surprising that ML approaches, as novel and efficient tools to mine the useful knowledge from data, have created inroads in a diversity of scopes of TCM over the past decade of years. However, by browsing lots of literature, we find that not all of the ML approaches perform well in the same field. Upon further consideration, we infer that the specificity may inhere between the ML approaches and their applied fields. This systematic review focuses its attention on the four categories of ML approaches and their eight application scopes in TCM. According to the function, ML approaches are classified into four categories, including classification, regression, clustering, and dimensionality reduction, and into 14 models as follows in more detail: support vector machine, least square-support vector machine, logistic regression, partial least squares regression, k-means clustering, hierarchical cluster analysis, artificial neural network, back propagation neural network, convolutional neural network, decision tree, random forest, principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis. The eight common applied fields are divided into two parts: one for TCM, such as the diagnosis of diseases, the determination of syndromes, and the analysis of prescription, and the other for the related researches of Chinese herbal medicine, such as the quality control, the identification of geographic origins, the pharmacodynamic material basis, the medicinal properties, and the pharmacokinetics and pharmacodynamics. Additionally, this paper discusses the function and feature difference among ML approaches when they are applied to the corresponding fields via comparing their principles. The specificity of each approach to its applied fields has also been affirmed, whereby laying a foundation for subsequent studies applying ML approaches to TCM. [ABSTRACT FROM AUTHOR]

UHPLC combined with Fourier‐transform ion cyclotron resonance MS metabonomic approach was employed to screen the differential components between normal rats and yeast‐induced pyrexia rats after an oral administration of Gegenqinlian decoction (GQLD). Nine compounds, namely puerarin, daidzein, baicalin, wogonoside, wogonin, berberine, palmatine, jateorhizine, and coptisine, were identified as differential components in the plasma. A rapid, sensitive, selective, and accurate UHPLC–MS method was developed and fully validated for the simultaneous determination of the screened components in rat plasma after an oral administration of GQLD. The values for the limit of quantification ranged from 0.025 to 5.0 ng/mL. The inter‐ and intra‐day precision of all analytes was ≤10.7%, with an accuracy of ≤10.5%. Good extraction recovery and matrix effects were also obtained. The method was successfully applied to a comparative pharmacokinetic study of GQLD in normal and pyrexia rats. The results showed that the pharmacokinetic behavior of the analytes was changed in pyrexia rats compared to normal rats. These results could provide beneficial guidance for clinical applications of GQLD. [ABSTRACT FROM AUTHOR]

Background and Objective: HEC30654 is a selective 5-HT6 receptor antagonist that was safe and well-tolerated in preclinical models of Alzheimer's disease. The objective of this double-blind, randomized, placebo-controlled clinical trial was to evaluate the safety, tolerability, and pharmacokinetic profile of HEC30654 after single ascending doses in healthy Chinese subjects. Methods: Healthy volunteers received a single oral dose of HEC30654 (5, 10, 15, 30, 60 mg). Safety and tolerability assessments included adverse events, vital signs, and findings on electrocardiograms, electroencephalograms, physical examination, and clinical laboratory tests. Pharmacokinetic analysis of HEC30654 and its major metabolite HEC93263 were conducted in blood, urine, and fecal samples. Results: Single doses of HEC30654 up to 30 mg were generally safe and well tolerated, but dose escalation was terminated early as the 60 mg HEC30654 treatment group met the pre-defined stopping rules specified in the protocol. Median tmax of HEC30654 was 6 h (range, 4–12 h), t1/2 of 10–60 mg HEC30654 ranged from 52.1 to 63.8 h. Exposure to HEC30654 across the dose range explored in this study increased more than in proportion to dose. Metabolism of HEC30654 to HEC93263 was slow (<10%), and HEC30654 was mainly eliminated unchanged through feces. Conclusion: Single doses of HEC30654 up to 30 mg were generally safe and well tolerated. Based on preclinical efficacy in various models of cognition, HEC30654 may represent a therapeutic option for symptomatic treatment of cognitive disorders. [ABSTRACT FROM AUTHOR]

Tiamulin fumarate (TIF) is a pleuromutilin antibiotic and has high activity against animal bacterial pathogens including aquatic bacterial pathogens. However, its pharmacokinetic profiles, tissue distribution characteristics and bioavailability in aquatic animals remain unknown. The objective of this study was to investigate the pharmacokinetics and tissue distribution regularities of TIF in tilapia (Oreochromis niloticus) following a single oral (PO) dose of 20 mg/kg body weight (bw) and a single intravenous (IV) dose of 5 mg/kg bw at 22 ± 1°C, respectively. TIF concentrations in tilapia plasma and tissues were determined using the isotope dilution HPLC‐HESI‐MS/MS procedure, which was validated according to the guidelines defined by US Food and Drug Administration. TIF was well distributed throughout the body compartments of tilapia judged by the apparent volume of distribution (Vd) >1 L/kg (6.69 L/kg PO and 1.78 L/kg IV). TIF had a short mean residence time (MRT; 22.82 h PO and 14.61 h IV) and quick total body clearance (CLb) (0.62 L kg−1 h−1 PO and 0.60 L kg−1 h−1 IV). The total area under the curve (AUCtot) of plasma were 32.25 μg h−1 ml−1 (PO) and 8.30 μg h−1 ml (IV), respectively, and the oral absolute bioavailability (F%) of TIF was calculated to be approximately 97.1%. For tissue distribution, high concentrations of TIF were found in kidney, and the longest MRT was recorded in bile. The withdrawal time (WT) of TIF in muscle, skin, liver, kidney, gill, and bile was 3.75 (4) and 1.79 (2), 1.77 (2) and 2.06 (3), 6.41 (7) and 1.97 (2), 6.95 (7) and 3.98 (4), 4.92 (5) and 2.36 (3), and 7.06 (8) and 6.16 (7) days after PO and IV administration, respectively. The present investigations indicated that TIF was quickly absorbed, well distributed, rapidly eliminated in tilapia, and it could serve as reference data for establishing use regimen and provide useful information for the further development of TIF in aquaculture. [ABSTRACT FROM AUTHOR]

Breviscapine is one of the extracts of several flavonoids of Erigeron breviscapus. Scutellarin is the main active component of breviscapine, and the qualitative or quantitative criteria as well. Scutellarin and its analogs share a similar skeleton of the flavonoids. Breviscapine has been widely used in the treatment of cerebral infarction and its sequelae, cerebral thrombus, coronary heart disease (CHD), and angina pectoris. Breviscapine has a broad spectrum of pharmacological activities, such as increasing blood flow, improving microcirculation, dilating blood vessels, decreasing blood viscosity, promoting fibrinolysis, inhibiting platelet aggregation, and thrombosis formation, etc. In addition, breviscapine and its analogs have significant value for drug research and development because of the superiority of those significant bioactivities. Furthermore, an increasing number of pharmacokinetic studies have explored the mechanism of scutellarin and its analogs. To provide a comprehensive understanding of the current research on breviscapine, scutellarin, and the analogs, the structural features, distribution situation, preparation method, content determination method, clinical applications, pharmacological action as well as pharmacokinetics are summarized in the present review. [ABSTRACT FROM AUTHOR]