Physalis alkekengi L. var. franchetii combined with hormone therapy for atopic dermatitis.

Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese medicine, is primarily used for the clinical treatment of AD. In this study, a 2,4-dinitrochlorobenzene-induced AD BALB/c mouse model was established, and a comprehensive pharmacological method was used to determine the pharmacological effects and molecular mechanisms of PAF in the treatment of AD. The results indicated that both PAF gel (PAFG) and PAFG+MF (mometasone furoate) attenuated the severity of AD and reduced the infiltration of eosinophils and mast cells in the skin. Serum metabolomics showed that PAFG combined with MF administration exerted a synergistic effect by remodeling metabolic disorders in mice. In addition, PAFG also alleviated the side effects of thymic atrophy and growth inhibition induced by MF. Network pharmacology predicted that the active ingredients of PAF were flavonoids and exerted therapeutic effects through anti-inflammatory effects. Finally, immunohistochemical analysis confirmed that PAFG inhibited the inflammatory response through the ERß/HIF-1α/VEGF signaling pathway. Our results revealed that PAF can be used as a natural-source drug with good development prospects for the clinical treatment of AD.

Inhibition of inflammasome activation via sphingolipid pathway in acute lung injury by Huanglian Jiedu decoction: An integrative pharmacology approach.

BACKGROUND: Acute lung injury (ALI) is a serious health issue which causes significant morbidity and mortality. Inflammation is an important factor in the pathogenesis of ALI. Even though ALI has been successfully managed using a traditiomal Chinese medicine (TCM), Huanglian Jiedu Decoction (HLD), its mechanism of action remains unknown. PURPOSE: This study explored the therapeutic potential of HLD in lipopolysaccharide (LPS)-induced ALI rats by utilizing integrative pharmacology. METHODS: Here, the therapeutic efficacy of HLD was evaluated using lung wet/dry weight ratio (W/D), myeloperoxide (MPO) activity, and levels of tumor necrosis factor (TNF-α), interleukin (IL)-1ß and IL-6. Network pharmacology predictd the active components of HLD in ALI. Lung tissues were subjected to perform Hematoxylin-eosin (H&E) staining, metabolomics, and transcriptomics. The acid ceramidase (ASAH1) inhibitor, carmofur, was employedto suppress the sphingolipid signaling pathway. RESULTS: HLD reduced pulmonary edema and vascular permeability, and suppressed the levels of TNF-α, IL-6, and IL-1ß in lung tissue, Bronchoalveolar lavage fluid (BALF), and serum. Network pharmacology combined with transcriptomics and metabolomics showed that sphingolipid signaling was the main regulatory pathway for HLD to ameliorate ALI, as confirmed by immunohistochemical analysis. Then, we reverse verified that the sphingolipid signaling pathway was the main pathway involed in ALI. Finally, berberine, baicalein, obacunone, and geniposide were docked with acid ceramidase to further explore the mechanisms of interaction between the compound and protein. CONCLUSION: HLD does have a better therapeutic effect on ALI, and its molecular mechanism is better elucidated from the whole, which is to balance lipid metabolism, energy metabolism and amino acid metabolism, and inhibit NLRP3 inflammasome activation by regulating the sphingolipid pathway. Therefore, HLD and its active components can be used to develop new therapies for ALI and provide a new model for exploring complex TCM systems for treating ALI.

Traditional Chinese medicines as effective agents against influenza virus-induced pneumonia.

Influenza virus-induced pneumonia (IVP) is a high morbidity and contagiousness pulmonary infectious disease caused by invasion of the influenza virus into the lower respiratory tract. Currently, the treatment of IVP is mainly based on an anti-influenza virus infection strategy, which includes the use of anti-influenza vaccines and drugs. However, the clinical use of these treatment options is limited as the influenza virus has a high level of variability and drug resistance may occur. Traditional Chinese medicines (TCMs) for the treatment of IVP have unique advantages, a variety of precise curative effects and have been widely used in clinical practice in China both historically and in the present day. However, there are only few literature reviews on the prevention and treatment of IVP using TCMs. Therefore, we conducted a review of relevant literature from the past 10 years and a comprehensive analysis of various databases containing reports on TCMs used for IVP prevention and treatment to provide basic data for future research and development of drugs against IVP. Herein, we summarize research progress on the pathogenesis of IVP, the TCMs effective in prevention or treatment of IVP, their underlying molecular mechanisms and active components. Overall, we provide a theoretical basis for the clinical use of TCM in the prevention and treatment of IVP. Furthermore, we provide a reference for the development of new multi-component, multi-target, low-toxicity drugs, which is of great academic and clinical significance.

Physalis alkekengi L. var. franchetii (Mast.) Makino: A review of the pharmacognosy, chemical constituents, pharmacological effects, quality control, and applications.

BACKGROUND: Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) (Chinese name Jin-Deng-Long) from the Solanaceae family is a traditional Chinese medicine with various pharmacological effects, such as removing heat, detoxification, improving throat conditions, removing phlegm, and ameliorating diuresis. PURPOSE: This paper reviews the existing literature and patents and puts forward some suggestions for future PAF research. METHODS: Using the PubMed, Google Scholar, Web of Science, and China National Knowledge Infrastructure databases, we performed comprehensive search of literature and patents published before April 2022 on PAF and its active ingredients. RESULTS: We comprehensively reviewed the research progress of PAF from aspects of the traditional application, botany, chemical composition, pharmacological effects, and toxicology, and first discussed quality control and modern applications, which have not been explored in previous reviews. Thereafter, we reviewed the limitations of pharmacological mechanism and quality control studies and proposed appropriate solutions, which is of great practical significance to subsequent studies. CONCLUSION: In this review, we present a comprehensive overview on PAF, and put forward new insights on studies regarding quality control, material basis, and mechanisms in classical prescription, providing theoretical guidance for the clinical application and development of Chinese medicine.

Integrative pharmacology reveals the mechanisms of Erzhi Pill, a traditional Chinese formulation, against diabetic cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhi Pill (EZP) is a traditional Chinese prescription that has marked effects in treating type 2 diabetes mellitus and diabetic nephropathy. However, its underlying pharmacological mechanisms in the treatment of diabetic cardiomyopathy (DCM), remain to be elucidated. AIM OF THE STUDY: This study aimed to apply an integrative pharmacological strategy to systematically evaluate the pharmacological effects and molecular mechanisms of EZP, and provide a solid theoretical basis for the clinical application of EZP in the treatment of DCM. MATERIALS AND METHODS: In this study, the potential targets and key pathways of EZP were predicted and validated using network pharmacology and molecular docking, respectively. Changes in cardiac metabolites and major metabolic pathways in rat heart samples were examined using 1H-nuclear magnetic resonance (NMR) metabolomics. Finally, biochemical analysis was conducted to detect the protein expression levels of key pathways. RESULTS: We found that EZP decreased fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels, increased high-density lipoprotein (HDL) levels in the serum, and alleviated the morphological abnormalities of the heart tissue in diabetic rats. Furthermore, EZP effectively restored superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspase-3, caspase-8, and caspase-9 activity levels, as well as the levels of reactive oxygen species (ROS), malondialdehyde (MDA), B-cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) in the heart tissue. Network pharmacology prediction results indicated that the mechanism of EZP in treating DCM was closely related to apoptosis, oxidative stress, and the HIF-1, PI3K-Akt, and FoxO signaling pathways. In addition, 1H-NMR metabolomics confirmed that EZP primarily regulated both energy metabolism and amino acid metabolism, including the tricarboxylic acid (TCA) cycle, ketone bodies metabolism, glutamine and glutamate metabolism, glycine metabolism, and purine metabolism. Finally, immunohistochemistry results indicated that EZP reduced the expression levels of p-AMPK, p-PI3K, p-Akt, and p-FoxO3a proteins, in the heart tissue of DCM rats. CONCLUSION: The results confirmed that the overall therapeutic effect of EZP in the DCM rat model is exerted via inhibition of oxidative stress and apoptosis, alongside the regulation of energy metabolism and amino acid metabolism, as well as the AMPK and PI3K/Akt/FoxO3a signaling pathways. This study provides an experimental basis for the use of EZP in DCM treatment.

Identification of active compounds and molecular mechanisms of Dalbergia tsoi Merr.et Chun to accelerate wound healing.

As a traditional Chinese medicine, Dalbergia tsoi Merr.et Chun (JZX) has been used for the treatment of wounds since ancient times. However, the active compounds and molecular mechanisms of JZX in the acceleration of wound healing are still unknown. Herein, we explored the main active compounds and key molecular mechanisms by which JZX accelerates wound healing. The ethanol extract of JZX was subjected to UPLC-Q-Orbitrap HRMS analysis to identify the main compounds. The pharmacological effect of JZX on wound healing was evaluated using a mouse excision wound model. Network pharmacology was utilized to predict the effective compounds and related signal transduction pathways of JZX that were involved in accelerating wound healing. The predicted key signaling pathways were then validated by immunohistochemical analysis. Interactions between the active compounds and therapeutic targets were confirmed by molecular docking analysis. JZX accelerated wound healing, improved tissue quality, and inhibited inflammation and oxidative stress. Moreover, our results suggested that the active components of JZX, such as butin, eriodyctiol, and formononetin, are the key compounds that facilitate wound treatment. Our studies also indicated that JZX accelerated wound healing by regulating the PI3K/Akt signaling pathway and inducing the expression of TGF-ß1, FGF2, VEGFA, ECM1, and α-SMA at different stages of skin wound healing. The JZX extract accelerates wound healing by reducing inflammation and inhibiting oxidative stress, regulating the PI3K/Akt signaling pathway, and promoting the expression of growth factors, suggesting that JZX has potential clinical applicability in wound treatment.

White matter alterations in heart-kidney imbalance insomnia and Jiao-Tai-Wan treatment: A diffusion-tensor imaging study.

Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.

Physalin B ameliorates inflammatory responses in lipopolysaccharide-induced acute lung injury mice by inhibiting NF-κB and NLRP3 via the activation of the PI3K/Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalin B (PB) is an active constituent of Physalis alkekengi L. var. Franchetii, which is a traditional medicine for clearing heat and detoxification, resolving phlegm, and diuresis. It has been commonly applied to treat sore throat, phlegm-heat, cough, dysuria, pemphigus, and eczema. AIM OF STUDY: Physalin B has shown efficacy as an anti-acute lung injury (ALI) agent previously; however, its mechanisms of action remain unclear. In the present study, we established a lipopolysaccharide-induced septic ALI model using BALB/c mice to further confirm the therapeutic potential of PB and to assess the underlying molecular mechanisms. MATERIALS AND METHODS: We used 75% ethanol and macroporous resin for extraction, separation, and enrichment of PB. The LPS-induced ALI mouse model was used to determine anti-inflammatory effects of PB. The severity of acute lung injury was evaluated by hematoxylin and eosin staining, wet/dry lung ratio, and myeloperoxidase (MPO) activity in lung tissue. An automatic analyzer was used to measure the arterial blood gas index. Protein levels of pro-inflammatory cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung tissue was measured using an ELISA. Quantitative RT-PCR was used to measure changes in RNA levels of pro-inflammatory cytokines in the lungs. A fluorometric assay kit was used for determination of apoptosis-related factors to assess anti-apoptotic effects of PB. Western blotting was used to assess levels of key pathway proteins and apoptosis-related proteins. Connections between the pathways were tested through inhibitor experiments. RESULTS: Pretreatment with PB (15 mg kg-1 d-1, i.g.) significantly reduced lung wet/dry weight ratios and MPO activity in blood and BALF of ALI mice, and it alleviated LPS-induced inflammatory cell infiltration in lung tissue. The levels of pro-inflammatory factors TNF-α, IL-6, and IL-1ß and their mRNA levels in blood, BALF, and lung tissue were reduced following PB pretreatment. PB pretreatment also downregulated the apoptotic factors caspase-3, caspase-9, and apoptotic protein Bax, and it upregulated apoptotic protein Bcl-2. The NF-κB and NLRP3 pathways were inhibited through activation of the PI3K/Akt pathway due to PB pretreatment, whereas administration of PI3K inhibitors increased activation of these pathways. CONCLUSIONS: Taken together, our results suggest that the anti-ALI properties of PB are closely associated with the inactivation of NF-κB and NLRP3 by altering the PI3K/Akt pathway. Furthermore, our findings provide a novel strategy for application of PB as a potential agent for treating patients with ALI. To the best of our knowledge, this is the first study to elucidate the underlying mechanism of action of PB against ALI.

Two new 3-hexenol glycosides from the calyces of Physalis alkekengi var. franchetii.

Two new hexenol glycosides, (Z)-hex-3-en-1-ol O-ß-d-xylcopyranosyl-(1-6)-ß -d-glucopyranosyl-(1-2)-ß-d-glucopyranoside (1) and (E)-hex-3-en-1-ol O-ß-d-xylcopyranosyl-(1-6)-ß-d-glucopyranosyl-(1-2)-ß-d-glucopyranoside (2), were isolated from the 50% ethanol elution of macroporous resin of Physalis alkekengi var. franchetii. Their structures were established by detailed spectroscopic analysis, including extensive 2D-NMR data. This is the first time to report the (Z) and (E) 3-hexenol glycosides from Physalis alkekengi var. franchetii.

Cardioprotective effect exerted by Timosaponin Bâ ¡ through the regulation of endoplasmic stress-induced apoptosis.

BACKGROUND: Timosaponin BⅡ (TBⅡ), one of the primary bioactive compounds from Anemarrhena asphodeloides Bunge, possesses potential cardioprotective effects. However, the mechanism underlying TBⅡ-mediated cardioprotection, especially the involvement of endoplasmic reticulum stress, remains largely unknown. PURPOSE: This study was designed to evaluate the role of TBⅡ in myocardial injury protection and explore its possible mechanisms. METHODS: In vivo models of isoproterenol-induced myocardial injury and H2O2-induced cytotoxicty were established to investigate the effect of anti-myocardial injury of TBⅡ. The potential mechanisms were investigated in vitro and in vivo using multiple detection methods like electrocardiography, histo-pathological examination, JC-1 staining, TUNEL staining, ELISA technology, and western blot analysis. RESULTS: In vivo study revealed that TBⅡ improved electrocardiography and heart vacuolation, reduced myocyte apoptosis, and improved the antioxidant potential. In vitro investigation demonstrated that TBⅡ pretreatment inhibited ER stress-mediated apoptosis pathways. Further investigation of the underlying mechanisms revealed that TBⅡ prevented H2O2-induced H9c2 cardiomyocytes injury by the PI3K/Akt pathways, whereas the addition of LY294002, the pharmacologic antagonist of PI3K, attenuated TBⅡ-induced expression of apoptotic protein and cytoprotective effects. CONCLUSION: These results suggested that TBⅡ protects against myocardial injury in vitro and enhances cellular defense capacity by inhibiting ER stress-mediated apoptosis pathways in vivo by activating the PI3K/Akt pathways.

Systems pharmacology reveals the mechanism of activity of Ge-Gen-Qin-Lian decoction against LPS-induced acute lung injury: A novel strategy for exploring active components and effective mechanism of TCM formulae.

Acute lung injury (ALI), a severe and life-threatening inflammation of the lung, with high morbidity and mortality, underscoring the urgent need for novel treatments. Ge-Gen-Qin-Lian decoction (GQD), a classic Chinese herbal formula, has been widely used to treat intestine-related diseases in the clinic for centuries. In recent years, a growing number of studies have found that GQD has a favorable anti-inflammatory effect. With the further study on the viscera microbiota, the link between the lungs and the gut-the gut-lung axis has been established. Based on the theory of the gut-lung axis, we used systems pharmacology to explore the effects and mechanisms of GQD treatment in ALI. Hypothesizing that GQD inhibits ALI progression, we used the experimental model of lipopolysaccharide (LPS)-induced ALI in Balb/c mice to evaluate the therapeutic potential of GQD. Our results showed that GQD exerted protective effects against LPS-induced ALI by reducing pulmonary edema and microvascular permeability. Meanwhile, GQD can downregulate the expression of LPS-induced TNF-α, IL-1ß, and IL-6 in lung tissue, bronchoalveolar lavage fluid (BLAF), and serum. To further understand the molecular mechanism of GQD in the treatment of ALI, we used the network pharmacology to predict the disease targets of the active components of GQD. Lung tissue and serum samples of the mice were separately analyzed by transcriptomics and metabolomics. KEGG pathway analysis of network pharmacology and transcriptomics indicated that PI3K/Akt signaling pathway was significantly enriched, suggesting that it may be the main regulatory pathway for GQD treatment of ALI. By immunohistochemical analysis and apoptosis detection, it was verified that GQD can inhibit ALI apoptosis through PI3K/Akt signaling pathway. Then, we used the PI3K inhibitor LY294002 to block the PI3K/Akt signaling pathway, and reversely verified that the PI3K/Akt signaling pathway is the main pathway of GQD anti-ALI. In addition, differential metabolites in mice serum samples indicate that GQD can inhibit the inflammatory process of ALI by reversing the imbalance of energy metabolism. Our study showed that, GQD did have a better therapeutic effect on ALI, and initially elucidated its molecular mechanism. Thus, GQD could be exploited to develop novel therapeutics for ALI. Moreover, our study also provides a novel strategy to explore active components and effective mechanism of TCM formula combined with TCM theory to treat ALI.

Systems pharmacology reveals the mechanism of activity of Physalis alkekengi L. var. franchetii against lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is an important cause of mortality of patients with sepsis, shock, trauma, pneumonia, multiple transfusions and pancreatitis. Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) has been extensively used in Chinese folk medicine because of a good therapeutic effect in respiratory diseases. Here, an integrated approach combining network pharmacology, proton nuclear magnetic resonance-based metabolomics, histopathological analysis and biochemical assays was used to elucidate the mechanism of PAF against ALI induced by lipopolysaccharide (LPS) in a mouse model. We found that the compounds present in PAF interact with 32 targets to effectively improve the damage in the lung undergoing ALI. We predicted the putative signalling pathway involved by using the network pharmacology and then used the orthogonal signal correction partial least-squares discriminant analysis to analyse the disturbances in the serum metabolome in mouse. We also used ELISA, RT-qPCR, Western blotting, immunohistochemistry and TUNEL assay to confirm the potential signalling pathways involved. We found that PAF reduced the release of cytokines, such as TNF-α, and the accumulation of oxidation products; decreased the levels of NF-κB, p-p38, ERK, JNK, p53, caspase-3 and COX-2; and enhanced the translocation of Nrf2 from the cytoplasm to the nucleus. Collectively, PAF significantly reduced oxidative stress injury and inflammation, at the same time correcting the energy metabolism imbalance caused by ALI, increasing the amount of antioxidant-related metabolites and reducing the apoptosis of lung cells. These observations suggest that PAF may be an effective candidate preparation alleviating ALI.

Advances in research into the mechanisms of Chinese Materia Medica against acute lung injury.

Acute lung injury (ALI) is a common and serious disease. Numerous treatment options are available but they do not improve quality of life or reduce mortality for ALI patients. Here, we review the treatments for ALI to provide basic data for ALI drug therapy research and development. Chinese Materia Medica (CMM) has long been the traditional clinical approach in China for the treatment of ALI and it has proven efficacy. The continued study of CMM has disclosed new potential therapeutic ingredients for ALI. However, few reviews summarize the currently available CMM-based anti-ALI drugs. Therefore, the systematic analysis of research progress in anti-ALI CMM is of great academic and clinical value. The aim of the present review is to describe CMM-based research progress in ALI treatment. Data were compiled by electronic retrieval (CNKI, SciFinder, PubMeds, Google Scholar, Web of Science) and from articles, patents and ethnopharmacological literature in university libraries were systematically studied. This review introduces progress in research on the etiology and mechanisms of ALI, the anti-ALI theory and modes of action in traditional Chinese medicine (TCM), anti-ALI active constituents of CMM, research progress in experimental methods of CMM anti-ALI, the anti-ALI molecular mechanisms of CMM, the anti-ALI efficacy of CMM formulae, and the potential toxicity of CMM and the antidotes for it. Scholars have investigated the anti-ALI molecular mechanism of CMM from various direction and have made substantial progress. This research explored the above aspects, enriched the anti-ALI theory of CMM and established the clinical significance and developmental prospects of ALI treatment by CMM. Because of the high frequency of drugs such as glucocorticoids or antibiotics, Western medicine lacks the advantages of CMM in terms of overall anti-ALI efficacy. In the future, the development of CMM-based anti-ALI therapies will become a major trend in the field of ALI drug development. Successful clinical safety and efficacy validations will promote and encourage the use of CMM. It provides fundamental theoretical support for the discovery and use of CMM resources through the comprehensive analysis of various anti-ALI CMM report databases.

Cardioprotective effects of a Fructus Aurantii polysaccharide in isoproterenol-induced myocardial ischemic rats.

CALB-3, a purified acidic hetero-polysaccharide isolated from Fructus aurantii, has been shown to exert cardioprotective effects in vitro. Recently, we investigated the protective effects of CALB-3 on myocardial injury and its possible mechanisms of action using a rat model of myocardial ischemia. In this study, a myocardial ischemia model was established via intragastric administration of 2 mg/kg isoproterenol (ISO) to male Sprague-Dawley rats (200-220 g) daily for 3 days. We found that pretreatment with CALB-3 (50, 100, and 200 mg/kg, i.g.) daily for 21 days prevented ISO-induced myocardial damage, including improvement in electrocardiographic parameters, and decrease in serum cardiac enzymes, heart vacuolation, and TUNEL-positive cells. We used western blotting to identify the underlying mechanisms and determine the possible signal pathways involved. We found that CALB-3 pretreatment prevented apoptosis, increased the expression of antioxidant enzymes, and enhanced the binding of Nrf2 to the antioxidant response element. In addition, CALB-3 activated the phosphorylation of PI3K/Akt and ERK to increase the cytoprotective effect. Overall, our results show that CALB-3 is a promising polysaccharide for protecting against myocardial injury induced by ISO.

The Effect of Tanreqing Injection on the Pharmacokinetics of Sirolimus in Rats.

To evaluate the effect of Tanreqing injection on the pharmacokinetics of sirolimus in rats, a high performance liquid chromatography tandem mass spectrometry method was developed for sirolimus assay in whole blood. Calibration curve of sirolimus was acquired over a concentration ranging from 2.5 to 100 ng/mL with r2= 0.9955. The matrix effects and extraction recoveries of sirolimus ranged from 144% to 152% and from 80% to 96%, respectively. The inter- and intraday relative standard deviations were both <10%. The stability investigation showed that the blood samples were stable for 30-day-storage at -20°C, for 8 h storage at room temperature, for 24 h storage in the auto-sampler at 4°C, and for three freeze-thaw cycle process. The pharmacokinetic results demonstrated that the C max, AUC, and AUMC of sirolimus in rats (7.5 mg/kg, i.g.) were increased after beincoadministration with Tanreqing Injection at 2.5, 5.0, and 7.5 mL/kg (i.v.), respectively, or at 5 min, 2 h, and 4 h (5.0 mL/kg, i.v.) after SRL dosing, respectively. For the first time, the results proved the herb-drug interaction between Tanreqing Injection and sirolimus and accordingly suggested avoiding concurrent reception of those two drugs for patients.

Wuzhi capsule regulates chloroacetaldehyde pharmacokinetics behaviour and alleviates high-dose cyclophosphamide-induced nephrotoxicity and neurotoxicity in rats.

High-dose cyclophosphamide (HD-CTX) treatment often leads to severe nephrotoxicity and neurotoxicity, which are mainly caused by one of its metabolites, chloroacetaldehyde (CAA). However, there are no effective antidotes to prevent these side effects. The objective of this study was to evaluate the effect of Wuzhi Capsule (WZC) on the pharmacokinetics of CTX and its metabolites in rats, and the attenuation of CAA induced kidney and brain injuries, which was produced at equimolar with 2-dechloroethylcyclophosphamide. Rats were treated with single- or multiple-dose of WZC when giving HD-CTX, and the plasma concentration of CTX and its metabolites were quantitated by UHPLC-MS/MS Single-dose, not multiple-dose of WZC co-administration (300 mg/kg) significantly reduced Cmax and AUC0→24 h of DC-CTX by 33.10% and 35.51%, respectively. Biochemical assay suggested oxidative stress was involved in kidney and brain injuries by HD-CTX, which were attenuated by single-dose WZC (300 mg/kg) pre-treatment, with increased glutathione, glutathione peroxidase and superoxide dismutase contents/or activities in both tissues and plasma (P < 0.05). Meanwhile, WZC pre-treatment could also significantly decrease the plasma levels of creatinine, blood urea nitrogen and malondialdehyde (P < 0.05). Additionally, WZC treatment improved the morphology and pathology condition of the kidneys and brains in rats. In conclusion, single-dose WZC co-administration decreased CAA production and exerted protective effect on CTX-induced oxidative stress in kidney and brain, whereas repetitive WZC co-administration with CTX was probably not recommended.