Effects of Momordica charantia L. supplementation on glycemic control and lipid profile in type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials.

Background and aims: Momordica charantia L. (M. charantia) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM. Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals. Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: -0.85 mmol/L; 95%CI: -1.44, -0.26; p = 0.005; I2 = 73.4 %), postprandial glucose (PPG) (WMD: -2.28 mmol/L; 95%CI: -3.35, -1.21; p = 0.000; I2 = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.38 %; 95%CI: -0.53, -0.23; p = 0.000; I2 = 37.6 %), and total cholesterol (TC) (WMD: -0.38 mmol/L; 95%CI: -0.70, -0.07; p = 0.017; I2 = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results.

Radix Salvia miltiorrhiza Ameliorates Burn Injuries by Reducing Inflammation and Promoting Wound Healing.

Purpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats. Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue. Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-ß, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-ß1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney. Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.

Transcriptomic analysis the mechanisms of anti-osteoporosis of desert-living Cistanche herb in ovariectomized rats of postmenopausal osteoporosis.

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis.

Effects of whole-body vibration on sensorimotor deficits and brain plasticity among people with chronic ankle instability: a study protocol for a single-blind randomized controlled trial.

BACKGROUND: Chronic ankle instability (CAI) is a form of musculoskeletal disease that can occur after a lateral ankle sprain, and it is characterized by pain, recurrent ankle sprains, a feeling of "giving way" at the ankle joint, and sensorimotor deficits. There has been increasing evidence to suggest that plastic changes in the brain after the initial injury play an important role in CAI. As one modality to treat CAI, whole-body vibration (WBV) has been found to be beneficial for treating the sensorimotor deficits accompanying CAI, but whether these benefits are associated with brain plasticity remains unknown. Therefore, the current study aims to investigate the effect of WBV on sensorimotor deficits and determine its correlation with plastic changes in the brain. METHODS: The present study is a single-blind randomized controlled trial. A total of 80 participants with CAI recruited from the university and local communities will be divided into 4 groups: whole-body vibration and balance training (WBVBT), balance training (BT), whole-body vibration (WBV), and control group. Participants will be given the WBV intervention (25-38 Hz, 1.3-2 mm, 3-time per week, 6-week) supervised by a professional therapist. Primary outcome measures are sensorimotor function including strength, balance, proprioception and functional performance. Brain plasticity will be evaluated by corticomotor excitability, inhibition, and representation of muscles, as measured by transcranial magnetic stimulation. Activation of brain areas will be assessed through functional near-infrared spectroscopy. Secondary outcome measures are self-reported functional outcomes involving the Cumberland Ankle Instability Tool and the Foot and Ankle Ability Measure. All tests will be conducted before and after the WBV intervention, and at 2-week follow-up. Per­protocol and intention-to-treat analysis will be applied if any participants withdraw. DISCUSSION: This is the first trial to investigate the role of brain plasticity in sensorimotor changes brought by WBV for individuals with CAI. As plastic changes in the brain have been an increasingly important aspect in CAI, the results of the current study can provide insight into the treatment of CAI from the perspective of brain plasticity. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300068972); registered on 02 March 2023.

Synthesis, characterization and anti-breast cancer activities of stachydrine derivatives.

Stachydrine is a hydrophilic quaternary amine salt with good antitumor effect, but its application is limited due to its rapid metabolism and low bioavailability. We synthesized and evaluated nine prodrugs of stachydrine, which showed suitable hydrophobicity (CLogP: -2.58-4.78, vs SS-0: -3.32) and better in vitro anticancer activity (IC50: 0.34 µM-14.03 mM, vs SS-0: 38.97 mM-147.19 mM) in comparison with stachydrine. Among them, SS-12, SS-16 and SS-18 are the most effective compounds against 4T1 cells, and the IC50 is 2.15-24.14 µM. Especially, compared with stachydrine, SS-12 significantly blocked the cell cycle in the G0/G1 phase, reduced the mitochondrial membrane potential, and induced the apoptosis of 4T1 cells through mitochondria pathway, which increased the expressions of Bax and cleaved caspase-3 protein, decrease the expression of Bcl-2. The pharmacokinetics of SS-12 showed a rational bioavailability (79.6%), and a longer retention time (T1/2 = 7.62 h) than that of stachydrine (T1/2 ≈ 1.16 h) in rats. Compared with stachydrine, SS-12 significantly enhanced the anticancer efficacy (56.32% of tumor-inhibition rates, vs SS-0: 3.89%), meanwhile, ameliorated the tumor-induced organ damage in mice. Therefore, SS-12 may be a promising prodrug of stachydrine against breast cancer.

Role of the HIF-1α/BNIP3 Signaling Pathway in Recurrent Hepatocellular Carcinoma and the Mechanism of Traditional Chinese Medicine.

Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.

Association between sports participation and overall health in children and adolescents.

Emerging evidence revealed that participating in sports may have benefits for health, but the association between sports participation and self-rated overall health has not been clearly established in children and adolescents. The present study aimed to examine the cross-sectional relationships between sports participation and self-rated overall health. A national sample of 42,777 (mean age = 9.4 ± 5.2, 48.3% girls) United States children and adolescents completed self-administered questionnaires and were included in the final analysis. The crude and adjusted odds ratio (ORs) and 95% CI were used to analyze the association between sports participation and self-rated overall health. Results indicated that children and adolescents participated in sports were more likely to report better overall health (OR = 1.92, 95%CI: 1.83, 2.02) compared to those not participating in sports. This study found that sport participation was positively associated with self-rated overall health in children and adolescents. This study offers evidence concerning adolescents' health literacy promotion.

Postmenopausal osteoporosis: a bioinformatics-integrated experimental study the pathogenesis.

Postmenopausal osteoporosis (PMOP) is a chronic bone metabolic disease, which often causes fractures and various complications, it causes a great social and economic burden, and it is urgent to use modern research techniques to elucidate the pathogenesis of PMOP. At the same time, because of the complex physiological and pathological interaction mechanism between osteoporosis and sarcopenia, the correlation research has become a hot topic. Ovary removal is a commonly used experimental method to study the endocrine system of female animals, and it is also the best animal model to study PMOP. In this study, the preparation of the ovariectomized rat was confirmed through the detection of vaginal smear, the level of bone formation markers, and the analysis of bone tissue morphology. Transcriptome sequencing was used to analyze the molecular mechanism of PMOP in ovariectomized rats, qRT-PCR was used to verify the key targets. Results of Micro-CT and scanning electron microscopy (SEM) showed that the trabecular structure was disorganized and the symptoms of osteoporosis appeared, this indicating that the ovariectomized rats model was successfully prepared. Transcriptional sequencing results of femur tissue showed that 452 differentially expressed genes (DEGs) were screened. Bioinformatics analysis results showed that the osteoporosis caused by ovariectomized rats was mainly related to muscle contraction, calcium signaling pathway, etc. Results of qRT-PCR were consistent with transcriptome analysis. These results reveal the pathogenesis of PMOP in ovariectomized rats and also offer a possibility for elucidating the relevance of action between PMOP and sarcopenia.

Novel Ascorbic Acid Co-Crystal Formulations for Improved Stability.

A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

Lifestyle Behaviors and Suicide-Related Behaviors in Adolescents: Cross-Sectional Study Using the 2019 YRBS Data.

Objective: The purpose of this research was to investigate the prevalence of lifestyle behaviors and suicide-related behaviors and the association between them using a nationally representative sample of adolescents from the USA. Methods: 13,677 high school students aged 14-18 years were included in this cross-sectional study. The research data were retrieved from the Youth Risk Behavior Surveillance System Survey in 2019. All data on age, sex, grade, race, physical activity, television time, fruit intake, and suicide-related behavior were self-reported by students. Logistic regression models were adopted to examine the association between lifestyle behaviors and the suicide-related behaviors. Results: Students who played video/computer games for ≥2 h had higher risk of suicide attempt (OR = 1.55, 95%CI: 1.30-1.85). Daily sleep duration of ≤8 h was positively associated with considering a suicide attempt (OR = 1.99, 95%CI: 1.62-2.43). In addition, participants who did not engage in any sport team were more likely to report considering a suicide attempt (OR = 1.50, 95%CI: 1.24-1.81). Conclusion: This research suggests that some lifestyle behaviors (e.g., time for video or computer use, sleep duration, sports team participation, regular breakfast intake, and substance use) are associated with increased risk of suicidal behavior and ideation in high school students. To identify the specific effect of multiple lifestyle factors in influencing the risk of suicide-related behaviors in high school students, longitudinal studies are warranted in future.

Total flavonoids of Taraxacum mongolicum inhibit non-small cell lung cancer by regulating immune function.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum mongolicum Hand.-Mazz. has been used in lung cancer treatment in Chinese medicine. However, its specific mechanism of action has not yet been reported, and developing pharmaceutical anti-cancer resources is important. Here, we aimed to elucidate the anti-tumor effects of dandelion in vitro and in vivo and assess its effects on immune function in lung cancer patients. AIM OF THE STUDY: In the present study, we mainly observed the therapeutic effects of total flavonoids from Taraxacum mongolicum Hand.-Mazz. (TFTM) on non-small cell lung cancer and its influence on the body's immune function. MATERIALS AND METHODS: In vitro experiments on A549 and H1299 cells were performed using the CCK8 method; the proliferation and migration of cells were observed to investigate the wound healing effects of TFTM, and flow cytometry was used to detect the apoptotic rate of TFTM on lung cancer cells. In vivo experiments were preformed to establish a non-small cell lung cancer mouse model using subcutaneously transplanted Lewis cells, and the body weight and tumor growth of the mice were recorded. Hematoxylin and eosin staining was performed for tumor tissue to assess pathological changes. The thymus, spleen, and lungs were isolated for to calculate organ index. The CD4+, CD8+, and CD4+/CD8+ levels were detected in mouse spleen using flow cytometry, and IL-2, IL-3, IFN-γ, and TNF-α levels were determined in serum using enzyme-linked immunosorbent assay. Expressions of IL-2, IL-3, IFN-γ, and TNF-α were detected using quantitative real-time PCR in tumor tissues, and Ki67 expression was observed by immunofluorescence. RESULTS: At 24 h, TFTM (100 and 200 µg/mL) had the best inhibitory effect on the proliferation of A549 and H1299 cells. The cell migration rate significantly reduced (P < 0.01), and the tumor inhibition rate increased (P < 0.01) and promoted apoptosis (P < 0.01). The mouse thymus index significantly increased (P < 0.05) and mouse spleen index reduced (P < 0.05). The CD4+, CD8+, and CD4+/CD8+ levels in Lewis lung cancer mouse model increased, as did the levels of IL-2, IL-3, IFN-γ, and TNF-α in the serum and tumor of mice; Ki67 expression in tumor tissues significantly reduced (P < 0.01). CONCLUSION: TFTM has an inhibitory effect on lung cancer. The mechanism may be that it improves the host's protective immune response by having a milder tumor growth inhibitory effect than cyclophosphamide.

[Animal model analysis of diabetic lower extremity arterial disease based on clinical symptoms of traditional Chinese and Western medicine].

The evaluation standard of LEAD animal model was established according to the understanding of the etiology and pathogenesis of diabetic lower extremity vascular disease based on Chinese and Western medicine. The consistency between the existing LEAD animal model and the clinical characteristics of traditional Chinese and Western medicine was analyzed and evaluated. The advantages and disadvantages of the existing model were compared,the application scope of different models was considered,and the possible improvement methods of the existing model were proposed,so as to provide impetus for the improvement of LEAD animal model.We should reflect more characteristics of traditional Chinese medicine syndromes in the process of model improvement and development,making the LEAD animal model to get closer to clinical features of traditional Chinese and Western medicine.

[Analysis of animal models of chronic atrophic gastritis based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

Based on the clinical characteristics of chronic atrophic gastritis in traditional Chinese and Western medicine, the domestic and foreign relevant literature reports and animal models of chronic atrophic as well as the clinical diagnostic indicators of traditional Chinese and western medicine, chronic atrophic gastritis evaluation standard was summarized to evaluate and analyze the coincidence degree of clinical symptoms of the existing chronic atrophic gastritis animal models. The statistical results found that modeling methods with a higher coincidence degree with the existing chronic atrophic gastritis animal models are disease and syndrome combination mode-ling, surgical modeling, multifactor comprehensive modeling and MNNG modeling. Although the animal models were reproduced by such methods as etiology, pathogenesis and disease and syndrome combination similar to those of human beings, there is still a big gap with the natural disease state. Further in-depth studies and improvement shall be made in clinical practice in the hope to provide refe-rence for clinical practice and experimental studies of chronic atrophic gastritis.

Study on the anti-hepatocarcinoma effect and molecular mechanism of Prunella vulgaris total flavonoids.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of Prunella vulgaris is for the treatment of liver cancer in a few areas of China. At present, it is used primarily for the treatment of thyroid cancer, throat cancer, and lymphosarcoma among others. However, there are few current scientific reports regarding its use for the treatment of liver cancer. In this paper, the effective treatment for liver cancer is studied to provide an experimental basis for the application of Prunella vulgaris, which is related to preparations in the treatment of liver cancer. AIM OF THE STUDY: To study the anti-hepatocarcinoma effect of Prunella vulgaris total flavonoids and explores the possible molecular mechanism. METHODS: The effects of Prunella vulgaris total flavonoids on the proliferation of SMMC-7721 cells were respected by RTCA analysis system. The tumor volume and weight were found in H22 tumor bearing mice. ELISA was used to observe the apoptosis and autophagy protein expressions in tumor tissue homogenate, along with the immune serum factor. Tumor tissue apoptosis was respected by the TUNEL method. And Bax, Bcl2, PI3K, Akt, mTOR, Beclin-1 and LC3-I/LC3-II expression were observed through Western blot. We also observed the expression of Beclin-1 and LC3-I/LC3-II through immunohistochemistry. RESULTS: The total flavonoids of Prunella vulgaris inhibited the activity of SMMC-7721 cells, and reduced the tumor volume and weight in H22 tumor bearing mice. HE staining showed that the Prunella vulgaris total flavonoids inhibited liver metastasis of H22 tumor. The Prunella vulgaris total flavonoids significantly made the expressions of IL-6, TNF-α and IFN-γ immune factors increasing in the serum of tumor bearing mice, and the contents of caspase-3 and caspase-9 increase as well in tumor tissue homogenate. TUNEL showed that the mean density in the intervention group was significantly higher than that in the control group. P62 content in tumor tissue homogenate increased and ATG5 decreased after intervention. Immunohistochemistry showed Beclin-1 expression decreased and LC3-I/LC3-II increased in the tumor tissue. Western blot showed Bcl2, Beclin-1 expression decreased and Bax, PI3K, Akt, mTOR, LC3-I/LC3-II increased in the tumor tissue. CONCLUSION: Prunella vulgaris total flavonoids have an obvious anti-hepatocarcinoma effect, and the mechanism may be linked to the inhibition of autophagy and promotion of apoptosis in liver cancer cells. The inhibition of autophagy may be related to activation of the PI3K/Akt/mTOR pathway.

Effects of total flavonoids from Eucommia ulmoides Oliv. leaves on polycystic ovary syndrome with insulin resistance model rats induced by letrozole combined with a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. leaves are the dry leaves of Eucommia ulmoides Oliv. Modern studies have shown that Eucommia ulmoides Oliv. leaves and its extracts have many pharmacological effects, such as regulating hypothalamus pituitary ovary (HPO) axis function, estrogen like effects, correcting insulin resistance (IR), regulating lipids, and reducing weight, which are consistent with the clinical manifestations in polycystic ovary syndrome (PCOS) patients. PCOS patients often have HPO axis disorder, low estrogen, high androgen, high IR complication rate, and obesity. Previous preclinical studies have shown that total flavonoids from Eucommia ulmoides Oliv. leaves (TFEL) can improve the imbalance in sex hormone secretion in perimenopausal animal models by regulating the function of the HPO axis. Thus, it is important to understand if flavonoids are the active parts of Eucommia ulmoides Oliv. leaves that interfere with polycystic ovary syndrome with insulin resistance (PCOS-IR), and determine the regulatory role they play in sex hormones and IR? AIM OF THE STUDY: Investigate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the ovary and kisspeptin/insulin like growth factor/leptin receptor1/androgen receptor (Kiss1/IGF-1/LEPR/AR) in the HPO axis to determine the mechanism of TFEL intervention in a rat model of PCOS-IR model rats. MATERIALS AND METHODS: A rat model of PCOS-IR was established using a high-fat diet (49 d) combined with letrozole (1 mg/kg·d, for 28 d). Then, metformin (300 mg/kg·d) and TFEL (220 mg/kg·d, 110 mg/kg·d, and 55 mg/kg·d) were administered continuously for 21 days. At the end of the experiment, samples were taken and the related indexes were measured. RESULTS: TFEL reduced the body weight, Lee's index, ovarian index, ovarian area and ovarian volume, increased serum E2, SHBG levels and ISI, decreased serum levels of T, LEP, INS, and FBG (whole blood), and reduced the HOMA-IR in rats with PCOS-IR. TFEL downregulate Kiss1, IGF-1, and AR in the arcuate nucleus of hypothalamus, and upregulate Kiss1, downregulate IGF-1 and AR in the pituitary gland, and upregulate Kiss1, downregulate IGF-1, LEPR, and AR in the ovary of rats with PCOS-IR. TFEL could downregulate p-IRS-1Ser307, upregulate IRS-1, p-IRS-1Tyr895, PI3Kp85α, p-PI3Kp85α, AKT, p-AKT, and GLUT4 in the ovary, and ameliorated histopathological changes in the ovary and pancreas of rats with PCOS-IR. CONCLUSION: TFEL can inhibit ovarian hyperplasia, regulate disorders of glucose and lipid metabolism and improve the secretion of sex hormones, by regulating the expression of PI3K/AKT signaling pathway-related proteins in the ovary and Kiss1/IGF-1/LEPR/AR in the HPO axis.

Protection against acute cerebral ischemia/reperfusion injury by Leonuri Herba Total Alkali via modulation of BDNF-TrKB-PI3K/Akt signaling pathway in rats.

OBJECTIVE: To observe the brain protective effect of Leonuri Herba Total Alkali (LHA) on cerebral ischemia reperfusion injury in rats, so as to provide basis for clinical research. METHODS: Adult male SD rats were randomly assigned into sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, and LHA + MCAO/R group (25 mg/kg, 50 mg/kg, and 100 mg/kg). Fourteen days before MCAO/R surgery, the rats in treatment groups were orally administered with LHA in ultrapure water once daily for 14 days, while rats in the sham and MCAO groups were given the same amount of saline in advance. After 1 h of administration on the 14th day, MCAO surgery was subjected. The neurological deficits, brain infarct volume, histopathology, immunofluorescence, inflammation indicators and the gene/protein expressions of BDNF-TrKB-PI3K/Akt signaling pathway in the rat brain tissue were evaluated 24 h after the MCAO/R-injury. RESULTS: It was found that rats in LHA pre-administration group showed significantly reduced neurological deficit scores, infarction volume, the serum levels of NSE and S100ß. Meanwhile, the content of Evans Blue (EB) in brain tissue from LHA group was decreased, as well as the levels of inflammatory cytokines and their gene levels. Moreover, LHA pre-administration inhibited the expression of CD44, GFAP, FOXO1 and promoted the expression of BDNF and NeuN. In addition, LHA pre-administration could up-regulate the protein expression of TrkB, p-PI3K, p-Akt, Bcl-2, and down-regulate the protein expression of Bax, and increase the level of Bcl-2/Bax. CONCLUSIONS: The study demonstrated that LHA pre-administration could regulate the PI3K/Akt pathway by increasing BDNF levels, and play a neuroprotective role in cerebral ischemia-reperfusion injury.

Total glucosides of herbaceous peony (Paeonia lactiflora Pall.) flower attenuate adenine- and ethambutol-induced hyperuricaemia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbaceous peony (Paeonia lactiflora Pall.) flower has been used widely in dietotherapy in China and other countries. It has good ethnopharmacological value in the treatment of various metabolic diseases. However, the molecular mechanisms by which it lowers serum uric acid are unknown. The development of pharmaceutical resources is very important. Here, we sought to elucidate the mode of action of herbaceous peony in terms of reducing uric acid levels. AIM OF THE STUDY: In the present research, the effects of the total glucosides of herbaceous peony flower were investigated in a rat hyperuricaemia model. Another aim of the study was to clarify the mechanism by which herbaceous peony flower (TGPF) lowers serum uric acid levels. MATERIALS AND METHODS: A hyperuricaemic rat model was induced via intragastric administration of 100 mg/kg adenine and 250 mg/kg ethambutol hydrochloride (EH) for 23 d. Then TongFengShu 600 mg/kg, allopurinol 42 mg/kg, or TGPF (50 mg/kg, 100 mg/kg, or 200 mg/kg) was administered 1 h after the adenine and EH treatments. RESULTS: TGPF improved weight loss and decreased serum UA, XOD, MCP-1, TNF-α, Cr, and BUN in the rats with hyperuricaemic nephropathy. TGPF downregulated renal URAT1 and GLUT9, upregulated renal OAT1, and ameliorated histopathological changes in the thymus, spleen, and kidney. CONCLUSION: TGPF is promising as a therapeutic agent against hyperuricaemia. It regulates the uric acid transporters and diminished serum uric acid levels, and alleviates renal pathology associated with hyperuricaemia.