Natural Coptidis Rhizoma Nanoparticles Improved the Oral Delivery of Docetaxel.

Purpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.

Dissection of potential anti-osteoporosis mechanism of isopsoralen - a quality control marker in Psoraleae Fructus - by metabolite profiling and network pharmacology.

RATIONALE: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development. METHODS: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology. RESULTS: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.

Rehydration effect of qingshu buye decoction on exercise and high temperature-induced dehydration.

OBJECTIVE: The aim of this study was to conduct a comprehensive evaluation of the rehydration efficacy of QSBYD and elucidate its potential underlying mechanism. DESIGN: 38 participants were randomly assigned to receive either QSBYD or placebo before and after exercise and heat-induced dehydration. Hydration indicators were measured over time. Blood tests assessed cellular anaerobic respiration metabolites, serum inflammatory markers, and coagulation markers. Perceptual measures of thirst, fatigue, and muscular soreness were also taken. RESULTS: QSBYD consumption resulted in lower urine volume (Control vs. QSBYD: 260.83 ± 167.99 ml vs. 187.78 ± 141.34 ml) and smaller decrease in percentage of nude body weight change from baseline (Control vs. QSBYD: -0.52 ± 0.89% vs. -0.07 ± 0.52%). Although no significant differences in urine specific gravity, QSBYD resulted in reduced urine volume at 120 min, suggesting improved fluid retention. Furthermore, QSBYD resulted in lower levels of IL-1ß (Control vs. QSBYD: 2.40 ± 0.68 vs. 1.33 ± 0.66 pg/mL), suggesting QSBYD may provide benefits beyond hydration. CONCLUSION: Further investigation into the underlying mechanisms and long-term effects of QSBYD on hydration is warranted. QSBYD may be an effective alternative to commercial sports drinks in mitigating dehydration effects.

Design and Evaluation of Ophthalmic Thermosensitive In Situ Gel of Compound Salvia.

The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.

Characterization of chemical constituents and metabolites in rat plasma after oral administration of Ainsliaea fragrans Champ by using UHPLC-QTOF-MS/MS.

Ainsliaea fragrans Champ, a strong heat-clearing and detoxifying traditional Chinese medicine, has been effectively used for treating chronic cervicitis, endometritis, pelvic inflammatory diseases, and other conditions caused by damp heat. It shows a good effect in the treatment of cervicitis and has broad clinical application prospects. Nevertheless, there is no comprehensive study on its in vivo and in vitro chemical analysis. UHPLC-QTOF-MS/MS combined with the non-targeted characteristic filter analysis were used to conjecture and characterize the chemical components and in vivo metabolites of rats following oral administration of Ainsliaea fragrans Champ. In this study, A total of 85 compounds were identified in Ainsliaea fragrans Champ, including 29 flavonoids, 14 sesquiterpenoids, 25 chlorogenic acids, and 17 other compounds. In the plasma of rats after administration of Ainsliaea fragrans Champ, 160 compounds were deduced (19 prototype compounds and 141 metabolites). The 141 metabolites consist of 50 flavonoids, 80 phenolic acids and 11 Chlorogenic acids. The related metabolic pathways mainly involved demethylation, reduction, sulfonation, decarboxylation, hydroxylation, methylation, and glucuronide conjunction. In summary, the chemical components and metabolites of Ainsliaea fragrans Champ were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Ainsliaea fragrans Champ efficacy and theoretical support for illustrating the mechanism of medical action and its clinical application.

Efficacy and safety of the traditional Chinese formula Shengjiang powder combined with conventional therapy in the treatment of diabetic kidney disease: a systematic review and meta-analysis.

Objective: To investigate the efficacy and safety of Shengjiang powder as a treatment for DKD. Methods: A comprehensive search was performed in eight databases from their inception to December 30, 2023, to identify relevant RCTs. The inclusion criteria were diagnosis of DKD and intervention including TCM that contained Shengjiang powder. Two researchers independently conducted literature screening and data extraction, utilizing the Rob2 tool and GRADE to assess the quality of the RCTs. Meta-analysis was carried out using RevMan 5.4.1 and Stata 15.0. Results: As a result of the search, 23 RCTs comprising 1,682 patients. The interventions resulted in significant reductions in all the assessed indicators: 24-h urinary protein, UAER, mALB, BUN, Scr, FBG, 2hPG, HbA1c, total cholesterol, and Triglycerides. Together the results showed that Shengjiang powder, in conjunction with conventional therapy, is an effective treatment of DKD. Subgroup analyses, considering duration, stage, blood glucose control levels, baseline blood glucose levels, and baseline Scr levels indicated that shorter duration treatment had a greater effect on UAER, 2hPG, and HbA1c. Additionally, Shengjiang powder was more effective in reducing 24-h urinary protein, Scr, and 2hPG in stage IV patients compared to corresponding values at other stages. However, with respect to FBG, the treatment was more effective in stage II/III. Shengjiang powder also, reduced Scr levels significantly in patients with higher baseline Scr and reduced urinary protein excretion with stricter blood glucose control. The interventions had additional lipid-regulating effects in cases with looser blood glucose control and led to a remarkable reduction in BUN and Scr levels in patients with FBG > 11.1 mmol/L. Conclusion: Shengjiang powder may supplement conventional therapy, thus benefiting DKD patients in terms of reducing urinary protein, stabilizing kidney function, and improving blood glucose and lipid metabolism. Considering the significant heterogeneity among studies and limited quality of some reports, our conclusions need to be further verified through analyses utilizing larger, multi-center samples of higher quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024490795.

The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial.

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .

Clinical effect of qingre bawei capsules combined with budesonide in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To assess the clinical effect of Qingre Bawei capsules combined with budesonide in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: The retrospective study was conducted at the Baoding No.1 Central Hospital, China, and comprised data of patients with acute exacerbation of COPD admitted between June 1, 2020, and June 30, 2022. The patients were divided into two groups based on treatment methods. The group A had been treated with Qingre Bawei capsules in combination with budesonide, while the group B had been treated with budesonide alone. Both the groups had been treated for 2 consecutive weeks. The changes in blood gas indicators, inflammation indicators, and lung function indicators were compared between two groups of patients before and 24 hours after treatment. The time for clinical symptom disappearance and adverse reactions between the two groups of patients was also noted. RESULTS: Of the 120 patients, 60(50%) were in group A; 41(68.3%) males and 19(31.7%) females, with mean age 65.28±4.36 years (range: 47-78 years) and mean course of disease 31.22±4.75 hours (range: 6-65 hours). 60(50%) patients were in group B; 43(71.7%) males and 17(28.3%) females with mean age 65.31±4.31 years (range: 48-78 years) and mean course of disease 31.29±4.71 hours (range: 8-68 hours). The disappearance time of clinical symptoms in group A was better than group B (p<0.05). The levels of blood gas indicators, inflammation indicators, and lung function indicators in both groups significantly improved (p<0.05), but the degree of improvement in group A was better than group B (p<0.05); The total effective rate of group A was better than group B (p<0.05). None of the patients in either group experienced any significant adverse reaction. CONCLUSIONS: Qingre Bawei capsules combined with budesonide had a significantly better therapeutic effect on cases of acute exacerbation of chronic obstructive pulmonary disease compared to budesonide alone.

Effects of Zishen Yutai pills combined with metformin on women with polycystic ovary syndrome undergoing in vitro fertilization.

In this study, we analyzed the clinical efficacy of Zishen Yutai pills (ZSYTP) combined with metformin hydrochloride on infertile women diagnosed with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET). Patients were assigned into 3 groups: the ZSYTP group (n = 50), the metformin group (n = 50), and the combination group (ZSYTP combined with metformin hydrochloride, n = 50), based on their respective and the indicated treatments before undergoing IVF-ET. Then, their glucose metabolism indices, sex hormone indices, traditional Chinese medicine (TCM) syndrome scores, and outcomes of IVF-ET were compared. Baseline characteristics were not significantly different between the 2 groups. After treatment, various parameters such as body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FIN), homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T) levels, and TCM syndrome scores were found to be reduced compared to pretreatment levels in both groups. Moreover, the improvement observed in the treatment group exceeded that of the control group. Specifically, the observation group displayed significantly lower gonadotropin (Gn) dosage and duration, as well as a reduced abortion rate compared to the control group. Furthermore, the observation group had higher numbers of obtained eggs, high-quality embryos, eggs obtained through IVF-ET, average transferred embryos, clinical pregnancy rate, and embryo implantation rate compared to the control group. Pretreatment with ZSYTP combined with metformin before IVF-ET in PCOS patients improves the outcome of IVF-ET.

Combination therapy of acupuncture and herbal medicine for heart failure: A systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) is characterized by functional or structural dysfunction of the heart, resulting in impaired blood ejection or ventricular filling. Conventional Western Medicine (CWM) remains the mainstay of treatment for HF; however, the occurrence of adverse events (AEs) necessitates the exploration of alternative treatments. Herbal medicine and acupuncture are adjunctive therapies for HF and have shown potential for improving heart function. This systematic review and meta-analysis aimed to assess the effectiveness and safety of acupuncture and herbal medicine in treating HF. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by National Institute of Informatics, KoreaMed, Research Information Sharing Service, and DBpia were searched for randomized controlled trials (RCTs) evaluating the effects of acupuncture and herbal medicine along with CWM as adjunctive treatments for HF, published from inception to May 31, 2024. Treatment effectiveness was determined by evaluating the left ventricular ejection fraction as the primary metric, along with the measurement of the total effective rate, brain natriuretic peptide level, N-terminal prohormone of brain natriuretic peptide level, left ventricular end-diastolic volume, and left ventricular end-systolic volume; the administration of the Minnesota Living with Heart Failure Questionnaire; and the conduct of a 6-minute walk test. Treatment safety was evaluated based on the incidence of AEs. The methodological quality of all included RCTs was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager, version 5.4.1. RESULTS: Of the 133 publications identified, 8 RCTs met the inclusion criteria. The meta-analysis showed significant improvements in left ventricular ejection fraction, brain natriuretic peptide levels, N-terminal prohormone of brain natriuretic peptide levels, left ventricular end-systolic volume, left ventricular end-diastolic volume, and 6-minute walk test results. Additionally, significant differences were observed in the total effective rate and Minnesota Living with Heart Failure Questionnaire responses. No significant medication-related AEs occurred in the intervention group. Conversely, 7 control patients developed well-known AEs associated with CWM. CONCLUSION: Acupuncture combined with herbal medicine and CWM is more effective than CWM alone, indicating a safe treatment approach. Consequently, the proactive administration of acupuncture alongside herbal medicine to patients with HF can be undertaken without concerns regarding AEs.

[Research progress on effect evaluation and application status of acupoint drug delivery].

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.

[Mechanism of Liangfang Wenjing Decoction in treatment of hypoxia on endometriosis with cold coagulation and blood stasis by regulating CHCHD4 expression].

To explore the mechanism of Liangfang Wenjing Decoction regulating coiled-coil-helix coiled-coil-helix domain containing 4(CHCHD4) in the treatment of hypoxia on endometriosis(EMs) with cold coagulation and blood stasis. The rat model of cold coagulation and blood stasis syndrome was prepared by the ice-water bath method, and then the EMs model was established by autologous intimal transplantation. The rats were randomly divided into model group, low, medium, and high(4.7, 9.4, and 18.8 g·kg~(-1)) dose groups of Liangfang Wenjing Decoction, Shaofu Zhuyu Decoction group, and sham group, with 10 rats in each group. The rats were given intragastric administration for four weeks. During the modeling, the general condition and vaginal smear of rats were observed, and the blood flow of ears and uterus were detected by laser speckle contrast imaging(LSCI) to judge the syndrome of cold coagulation and blood stasis. After the administration, the general condition of the rats was observed, and the area of ectopic lesions was measured by caliper. The localization and expression of CHCHD4 and hypoxia inducible factors-1α(HIF-1α) were detected by immunohistochemistry, and the mRNA and protein expressions of CHCHD4 and HIF-1α were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. The primary culture of ectopic endometrial stromal cells(ESCs) from EMs patients was performed, and the CHCHD4 overexpression plasmid was constructed and transfected to establish the ESCs model of CHCHD4 overexpression. The cells were divided into the control group, CHCHD4 overexpression group, CHCHD4 overexpression+control serum group, and CHCHD4 overexpression+Liangfang Wenjing Decoction serum group. The protein expression of CHCHD4 and HIF-1α was detected by Western blot, and the glucose consumption and lactic acid level were detected. The cell proliferation was detected by MTT assay. The experiment found that compared with normal rats, the modeling rats showed symptoms of cold coagulation and blood stasis, such as mental malaise, reduced diet and drinking water, disordered estrous cycle, and blocked blood circulation in ears and uterine microvessels. Compared with the sham group, the ectopic lesions in the model group were uplifted, and the mRNA and protein expressions of CHCHD4 and HIF-1α were significantly increased(P<0.05). Compared with the model group, the symptoms of cold coagulation and blood stasis in each treatment group were improved, and the area of ectopic lesions was significantly reduced(P<0.05 or P<0.01). The mRNA and protein expression levels of CHCHD4 and HIF-1α were significantly decreased(P<0.05 or P<0.01). In the cell model, compared with the control group, the expression of CHCHD4, HIF-1α protein, glucose consumption, lactic acid level, and cell proliferation activity in the CHCHD4 overexpression group were significantly increased(P<0.01). Compared with the CHCHD4 overexpression group, there was no significant change in each index in the control serum group, while the protein expression of CHCHD4 and HIF-1α in the Liangfang Wenjing Decoction serum group was decreased significantly(P<0.05 or P<0.01). The glucose consumption, lactic acid level, and cell proliferation activity decreased significantly(P<0.01). It can be seen from the above that the therapeutic effect of Liangfang Wenjing Decoction on EMs with cold coagulation and blood stasis might be related to reducing the expression of CHCHD4 and then improving the hypoxia of ectopic lesions and ectopic ESCs.

[Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on metabolomics].

In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E_2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E_2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.

[Metabolite identification and metabolic pathway analysis of Platycodonis Radix extracts from Tongcheng city in rats].

In this study, we delved into the prototypical components and metabolites of Platycodonis Radix extracts(PRE) from Tongcheng city in plasma, urine and feces of rats, and revealed its metabolic pathways and metabolic rules in vivo. The prototypical components and metabolites of PRE in rats were characterized and identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and mass defect filter(MDF). The biological samples were analyzed by ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm), with 0.1% formic acid water(A)-0.1% formic acid acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). Twelve prototypical saponins and twenty-seven metabolites were detected in plasma, urine and feces of rats treated with PRE by oral administration. Eleven prototypical components and nine metabolites were detected in plasma, eleven prototypical components and eight metabo-lites were detected in urine, and ten prototypical components and twenty metabolites were detected in feces. Further studies showed that the metabolic pathways of PRE in rats mainly include oxidation, reduction, acetylation, stepwise hydrolytic deglycosylation, glucuronidation and so on. This study provides a scientific basis for clarifying the pharmacological basis and mechanism of PRE from Tongcheng city.

[Effect of 2-phenylethyl-beta-glucopyranoside isolated from Huaizhong No. 1 Rehmannia glutinosa on hypoxic pulmonary hypertension by regulating PI3K/Akt/m TOR/HIF-1α pathway].

The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.

[Effect of Peitu Yifei Granules on autophagy mechanism in rats with idiopathic pulmonary fibrosis based on PI3K/Akt/mTOR signaling pathway].

To investigate the mechanism by which Peitu Yifei Granules inhibit idiopathic pulmonary fibrosis(IPF) in rats, fifty specific-pathogen-free(SPF) grade male Wistar rats were randomly divided into blank group and modeling group. IPF was induced in the modeling group rats by tracheal infusion of 5 mg·kg~(-1) bleomycin(BLM) and then randomly divided into model group, pirfenidone group, and high-dose, medium-dose, and low-dose groups treated with Peitu Yifei Granules. After 24 hours of modeling, the treatment groups received intragastric administration of either Peitu Yifei Granules or pirfenidone as a positive control drug; meanwhile, the model group received an equal volume of normal saline. After 21 days of treatment administration, lung tissue samples were collected for analysis. Pathological changes in lung tissues were assessed using hematoxylin-eosin(HE) staining and Masson's trichrome staining. The expression levels of protein kinase B(Akt), mammalian target of rapamycin(mTOR), their phosphorylated forms, and sequestosome 1(p62) were determined through Western blot(WB). Fluorescent quantitative real-time polymerase chain reaction(RT-qPCR) was used to measure messenger ribonucleic acid(mRNA) expression levels of Beclin-1, microtubule-associated proteins 1A/1B light chain 3B(LC3B), and p62. Immunohistochemistry was performed to assess protein expression levels of Beclin-1 and LC3B in lung tissue samples. RESULTS:: demonstrated that lung tissue structure appeared normal without significant collagen deposition in the blank group rats. In contrast, rats from the model group exhibited thickened alveolar septa along with evident inflammatory changes and collagen deposition. Compared to the model group rats, those treated with Peitu Yifei Granules or pirfenidone showed significantly improved lung tissue structure with reduced inflammation and collagen deposition observed histologically. Furthermore, compared with those of the blank group, the expressions of p62 and its mRNA, p-Akt and p-mTOR protein in lung tissues of the model group were significantly increased, while Beclin-1, LC3B and their mRNA levels were significantly decreased. Compared with those of the model group, the expressions of p62 and its mRNA, p-Akt and p-mTOR in lung tissues of the pirfenidone group and Peitu Yifei Granules high-dose and medium-dose groups were significantly decreased, while Beclin-1, LC3B and their mRNA expressions were significantly increased. The above results indicate that Peitu Yifei Granules can improve autophagy levels in lung tissues by inhibiting the phosphoinositide 3-kinase(PI3K)/Akt/mTOR signaling pathway and delay the development of IPF disease.

The antidepressant effect of Shexiang Baoxin Pills on myocardial infarction rats with depression may be achieved through the inhibition of the NLRP3 inflammasome pathway.

BACKGROUND: Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). METHODS: A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open-field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome-related protein expression via Western blotting and immunofluorescence. RESULTS: SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive-like behavior. Compared to the Sham group, levels of IL-1ß, IL-18, TNF-α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome-related proteins in the hippocampus revealed a significant upregulation of IL-1ß, IL-18, NLRP3, ASC, caspase-1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. CONCLUSION: We have observed a significant amelioration in depression-like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3-mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.).

Recognition of antitussive components in Farfarae Flos based on grey relational analysis and partial least squares regression. / åŸºäºŽç°è‰²å ³è”åº¦åˆ†æžå’Œåæœ€å°äºŒä¹˜å›žå½’è¾¨è¯†æ¬¾å†¬èŠ±æ­¢å’³æ´»æ€§æˆåˆ†.

OBJECTIVES: Farfarae Flos has the effect of cough suppression and phlegm elimination, with cough suppression as the main function. Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect, and some components have been confirmed to have cough suppressant activity. However, the antitussive material basis of Farfarae Flos has not been systematically elucidated. This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography (HPLC) fingerprint of Farfarae Flos extract with its cough suppressant activity. METHODS: HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data. Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract. SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups, a positive control group, and a blank control group (12 groups in total), with 10 guinea pigs in each group. The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10 (4 g/kg), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days. The guinea pigs were placed in 5 L closed wide-mouth bottles, and 17.5% citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes. The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig. Grey relational analysis (GRA) and partial least squares regression (PLSR) were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data, and predict the group of active ingredients in Farfarae Flos with antitussive activity. The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity: SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group, an active ingredient group, a positive control group, and a blank control group (4 groups in total), with 10 guinea pigs in each group. The S9 group was administered Farfarae Flos extract S9 (4 g/kg), the active ingredient group was administered the predicted combination of antitussive active ingredients (dose equivalent to 4 g/kg of Farfarae Flos extract S9), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days, and animal modeling and observation of efficacy indicators were the same as above. RESULTS: The HPLC fingerprint of 10 batches of Farfarae Flos extract was established, and the peak area data of 14 main common peaks were obtained. The antitussive effect data of 10 batches of Farfarae Flos extract were obtained. Compared with the blank control group, the cough latence in the positive control group and S1, S2, S3, S4, S6, S7, S8, S9, S10 groups was prolonged (all P<0.01), while the cough frequency in 5 minutes in the positive control group and S1, S2, S4, S6, S8, S9, S10 groups was decreased (all P<0.05). The analysis of spectrum-effect relationship revealed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercitrin, and rutin had high contribution to the antitussive effect of Farfarae Flos, and the 6 components were predicted to be the antitussive component group of Farfarae Flos. The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05), which confirmed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercetin, and rutin were the antitussive component group of Farfarae Flos. CONCLUSIONS: The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos. The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Determination of eleven components in rat plasma by UPLC-MS/MS and GC-MS for pharmacokinetic studies after oral administration of Citri Reticulatae Pericarpium extract.

Citri Reticulatae Pericarpium (CRP) is used as common health-care food and traditional Chinese medicine (TCM), which exerts pharmacological effects, such as anti-cardiovascular, anti-tumor, anti-oxidant, anti-inflammatory, anti-virus, hepatoprotective, blood pressure-lowering and neuroprotective. In this study, reliable, and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of eleven active components in rat plasma after oral administration of the CRP extract. The results of this method exhibited that the specificity, linearity (r > 0.999), precision and accuracy (the coefficient of variation (CV) < 11.5 %), recovery (52.9-107.9 %), matrix effects (63.8-107.5 %), and stability (CV < 10.8 %) met all requirements for the quantitation of plasma samples. The pharmacokinetic results showed that the Tmax of flavone glycosides was less than 0.7 h, and that of polymethoxyflavones and volatile components were within 1-7 h. Meanwhile, the area-under-the-curve (AUC) and concentration maximum (Cmax) of hesperidin, nobiletin, tangeretin, and D-limonene were higher than those of the other components, suggesting that the plasma exposure levels of these constituents were higher in CRP. The present research lays a foundation for elucidating the therapeutic material basis and provides a reference for further scientific research and clinical application of CRP.

Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.