Traditional Chinese Herbal Compound Research Articles

Cpd861 Targeting BCL2 to Alleviate Hepatic Fibrosis: Network Pharmacology, Mendelian Randomization, and Molecular Docking Mechanisms.

Compound 861 (Cpd861) is a traditional Chinese herbal compound for the treatment of hepatic fibrosis (HF). In the current investigation, Cpd861 has been demonstrated to have an underlying molecular mechanism and material foundation for the treatment of HF through network pharmacology, Mendelian randomization (MR), and molecular docking. Public databases were consulted for Cpd861 constituents and HF targets. Protein-protein interactions (PPIs) were established using STRING software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To elucidate the causal relationship between potential targets and liver injury, MR was used as a methodological tool. Finally, a molecular docking analysis was conducted between the active compound and the key target. We obtained 174 active ingredients and 113 intersecting genes. Through the PPI network, high-degree targets were identified, namely CTNNB1, ESR1, FOS, MDM2, CCND1, TP53, RELA, and BCL2. As shown by GO and KEGG pathway enrichment analyses, Cpd861 functions through xenobiotic stimulus and oxidative stress-related genes, as well as the PI3K-AKT and non-alcoholic fatty liver disease (NAFLD) signaling pathways. The results of MR showed that MDM2 and BCL2 had a causal relationship with liver injury. Molecular docking results showed that several active compounds in Cpd861 were stably bound to BCL2. This study made predictions regarding the efficacious components, as well as potential targets and pathways of Cpd861 in the therapy of HF. This will open up a new perspective for further investigation of the molecular mechanism of Cpd861 in the treatment of HF.

Traditional Chinese herbal compound as complementary treatment for nonspecific low back pain: A randomized controlled trial.

This prospective randomized controlled trial was designed to evaluate the clinical efficacy and safety of Bu Shen Tong Luo herbal compound as a complementary treatment for nonspecific low back pain (NSLBP). A total of 76 patients with NSLBP included from January 2022 to June 2023 according to the criteria were randomly divided into Bushen Tongluo formula (BSTL) group (n = 38) and celecoxib group (n = 38). According to Traditional Chinese Medicine principles, patients of 2 groups were divided into 5 syndrome types. Celecoxib or BSTL herbal compound were used to treat NSLBP of each group for 3 weeks, every week the Visual Analog Scale (VAS), Oswestry Disability Index, and Japanese Orthopaedic Association scores of each patient was record and compared to evaluate the clinical efficacy, and adverse reaction was reported to evaluate the safety of 2 interventions. A total of 71 patients finished the follow-up, including 36 patients in BSTL group and 35 patients in celecoxib group. The result showed that within 3 weeks, both BSTL and celecoxib interventions were able to treat NSLBP, with improvements in VAS scores and waist function index. However, there were no significant differences in clinical outcomes between these 2 interventions. Then we divided the patients into 5 syndromes on the basis of traditional Chinese medicine principles and observed their clinical outcomes. We found that celecoxib had similar improvements in VAS score and waist function index for each syndrome type and most of the syndromes in the BSTL group, except for the SRBZ syndrome. In the treatment of SRBZ syndrome, BSTL prescription showed no statistically significant clinical improvement. Meanwhile, in the treatment of HSBZ syndrome of NSLBP, BSTL prescription showed better clinical results than celecoxib, although there was no difference in VAS scores between the 2 groups, patients in BSXL group had better waist function than those in celecoxib group. Both BSTL herbal compound and celecoxib are effective and safe in the clinical treatment of NSLBP, and BSTL herbal compound had unique advantages in the treatment of HSBZ syndrome type of NSLBP especially in waist function improvement.

Rehmannia glutinosa DC.-Lilium lancifolium Thunb. in the treatment of depression: a comprehensive review and perspectives.

In recent years, the incidence of depression, recognized as a serious psychological disorder, has escalated rapidly. Rehmannia glutinosa DC. (Scrophulariaceae; Rehmanniae Radix, Crude drug) and Lilium lancifolium Thunb. (Liliaceae; Lilii bulbus, Crude drug) constitute a classic anti-depressant combination, exhibiting pharmacological effects that include anti-depressive, anti-anxiety, and anti-inflammatory properties. Current clinical studies have demonstrated that Baihe Dihuang Decoction, a traditional Chinese herbal compound, is effective in treating depression. However, the majority of scholars have predominantly examined Rehmannia glutinosa and Lilium in isolation, and a comprehensive elucidation of their principal active metabolites and pharmacological mechanisms remains lacking. A comprehensive literature search was conducted as of 29 September 2024, utilizing databases such as PubMed, CNKI, Wanfang Data, Baidu Scholar, and Google Scholar. Additionally, classical texts on Chinese herbal medicine, the Chinese Pharmacopoeia, as well as doctoral and master's theses, were included in the collected materials. The search employed specific terms including "R. glutinosa," "Lilium," "Baihe Dihuang decoction," "application of Baihe Dihuang decoction," "pathogenesis of depression," and "pharmacological action and mechanism of depression. This paper reviewed the traditional applications and dosages of the R. glutinosa-Lilium as documented in Chinese medical classics, thereby establishing a foundation for the contemporary development and clinical application of the classical formula Baihe Dihuang Decoction. Additionally, recent years have seen a comprehensive review of the pharmacological effects and mechanisms of R. glutinosa-Lilium and its principal metabolites in the context of depression. This paper has reviewed the active metabolites of R. glutinosa-Lilium and demonstrated its efficacy in the treatment of depression, as well as its role in modulating the underlying mechanisms of the disorder. The findings aim to serve as a reference for further research into the mechanisms of depression, its clinical applications, and the development of novel therapeutic agents.

Hippocampal PDHA1 gene knockout inhibits the Warburg effect leading to cognitive dysfunction and attenuates the beneficial effects of ZiBuPiYin recipe on cognition

Ethnopharmacological relevanceThe attenuation of the Warburg effect is an important pathological feature of cognitive dysfunction, and enhancing the Warburg effect is conducive to improving cognitive function. However, the pathogenic mechanisms underlying cognitive dysfunction remain incompletely elucidated. ZiBuPiYin Recipe (ZBPYR) is a traditional Chinese herbal compound used clinically for the treatment of cognitive dysfunction with significant efficacy. Nonetheless, the molecular mechanism underlying its beneficial effects remains elusive. Aim of the studyThe objective of this study is to investigate whether the attenuation of the Warburg effect exists in a mouse model of cognitive dysfunction induced by knockout of the pyruvate dehydrogenase E1 component subunit alpha (PDHA1) gene in the hippocampus, as well as the interventional effect of ZBPYR. Materials and methodsUsing mice with PDHA1 gene knockout in the hippocampus and their littermate control mice as study subjects, behavioral experiments were conducted to assess the impact of PDHA1 gene knockout on cognitive function and the interventional effect of ZBPYR. We detected the expression of the Warburg effect-associated rate-limiting enzymes and PI3K/AKT pathway-related proteins. Subsequently, in PC12 cells, we explored the effect of the Warburg effect on cell apoptosis as well as the role of PDHA1 in the regulation of the PI3K/AKT–Warburg effect and the potential mechanism of ZBPYR in improving cognitive function. ResultsMice with knockout of the PDHA1 gene in the hippocampus exhibited cognitive dysfunction, inhibition of the PI3K/AKT pathway, reduction of the Warburg effect, and neuronal damage. In vitro experiments indicated that silencing of PDHA1 in the hippocampus inhibited the PI3K/AKT–Warburg effect, leading to cell apoptosis and mediated the effect of ZBPYR in improving cognitive function. ConclusionOur data not only suggest that the hippocampal PDHA1-PI3K/AKT–Warburg effect may be involved in the pathogenesis of cognitive dysfunction, but also demonstrate that PDHA1 knockout can abolish the beneficial effects of ZBPYR on cognition. This research aids in unraveling the cause of cognitive dysfunction and, therefore, offers a promising and innovative therapeutic target for these patients.

Integrating serum metabolomics analysis and network pharmacology to reveal the potential mechanism of Shengmai Jianghuang San in the treatment of nasopharyngeal carcinoma.

Shengmai Jianghuang San (SMJHS) is a traditional Chinese herbal compound reported to inhibit Nasopharyngeal Carcinoma (NPC) progression and enhance radiosensitivity. However, the specific active ingredients and regulatory mechanisms of SMJHS against NPC, particularly under hypoxic conditions, remain unclear. In this study, Sprague-Dawley (SD) rats were gavaged with Shengmai Jianghuang San (SMJHS), and their blood was collected from the abdominal aorta. UHPLC-Q-Exactive orbitrap MS/MS was used to identify the metabolite profiles of SMJHS drug-containing serum. A molecular network of the active compositions in SMJHS targeting NPC was constructed through network pharmacology and molecular docking. The HIF-1α/VEGF pathway was in key positions. The effects of SMJHS on the proliferation, migration, and radiosensitivity of hypoxic NPC cells were assessed by in vitro experiments. NPC cell lines stably overexpressing HIF-1α were established using a lentivirus to investigate the regulation of HIF-1α/VEGF signaling in hypoxic NPC cells by SMJHS. Through a combination of network pharmacological analysis, cellular biofunctional validation, and molecular biochemical experiments, our study found that SMJHS had an anti-proliferative effect on NPC cells cultured under hypoxic conditions, inhibiting their migration and increasing their radiosensitivity. Additionally, SMJHS suppressed the expression of HIF-1α and VEGFA, exhibiting potential as an effective option for improving NPC treatment.

Huanglian-Hongqu herb pair improves nonalcoholic fatty liver disease via NF-κB/NLRP3 pathway in mice: network pharmacology, molecular docking and experimental validation

The Huanglian-Hongqu herb pair (HH) is a carefully crafted traditional Chinese herbal compound designed to address disorders related to glucose and lipid metabolism. Its primary application lies in treating hyperlipidemia and fatty liver conditions. This study explored the potential mechanism of HH in treating non-alcoholic fatty liver disease (NAFLD) through network pharmacology, molecular docking, and in vivo animal experiments. Ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UPLC-Q-TOF-MS) was employed to identify the chemical composition of HH. Network pharmacology was used to analyze the related signaling pathways affected by HH. Subsequently, the prediction was verified by animal experiment. Finally, we identified 29 components within HH. Network pharmacology unveiled interactions between HH and 153 NAFLD-related targets, highlighting HH’s potential to alleviate NAFLD through NF-κB signaling pathway. Molecular docking analyses illuminated the binding interactions between HH components and key regulatory proteins, including NF-κB, NLRP3, ASC, and Caspase-1. In vivo experiments demonstrated that HH alleviated NAFLD by reducing serum and liver lipid levels, improving liver function, and lowering inflammatory cytokine levels in the serum. Moreover, HH administration downregulated mRNA and protein levels of the NF-κB/NLRP3 pathway. In conclusion, our findings demonstrated that HH has potential therapeutic benefits in ameliorating NAFLD by targeting the NF-κB/NLRP3 pathway, facilitating the broader application of HH in the field of NAFLD.

Real-world effects of Yishen Tongbi decoction for rheumatoid arthritis: protocol for a prospective, observational, multicenter cohort study with validation against double-blind, randomized, controlled trial.

Introduction: Rheumatoid arthritis (RA) is a globally challenging and refractory autoimmune disease, constituting a serious menace to human health. RA is characterized by recurrent pain and is difficult to resolve, necessitating prolonged medication for control. Yishen Tongbi decoction is a traditional Chinese herbal compound prescribed for treating RA. We have completed a 3-year RCT study that confirmed the clinical efficacy of Yishen Tongbi decoction for RA. Notably, we observed a faster clinical remission rate compared to MTX by week 4 of treatment. In our forthcoming study, we intend to conduct a comprehensive assessment of the efficacy and safety of Yishen Tongbi decoction in the real-world treatment of RA through a prospective study. Methods and analysis: This prospective, multicenter, real-world observational study will be conducted at two designated centers in China from October 2023 to August 2025. The study will include 324 patients with active rheumatoid arthritis. One group will receive Yishen Tongbi decoction combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The other group will receive standard treatment. Standard treatment can be further divided into subgroups: csDMARDs, targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs). In each group, the number of tender joints, number of swollen joints, pain score, patient global assessment, physician global assessment, disease activity index (DAS28-ESR or DAS28-CRP), clinical disease activity index (cDAI), simplified disease activity index (sDAI) and relevant laboratory data will be compared. Clinical indicators and disease activity of the patients will be assessed at baseline, week 4 and week 12 after the initiation of treatment. The primary outcome will be the American College of Rheumatology 20% improvement criteria (ACR20) attainment rate among patients at week 12 after treatment. Every adverse event will be reported. Ethics and dissemination: This study has been approved by the Ethics Committee of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine (NO.K-2023-009). The results of the study will be published in national and international peer-reviewed journals and at scientific conferences. The researchers will inform participants and other RA patients of the results through health education. Clinical Trial Registration: https://www.chictr.org.cn/index.html, identifier ChiCTR2300076073.

Preparation and characterization of mixed-mode hydrophilic stationary phase based on triple hydrophilic functionalized moieties and its application to traditional Chinese herbal compound

In this paper, the surface modification of spherical silica was sequentially grafted with functional groups including imidazole, amide and sulfonic acid. The novel surface polymerization type stationary phases (SPs) for hydrophilic interaction liquid chromatography (HILIC) were obtained in three procedures. Elemental analysis, Fourier transform infrared spectroscopy, transmission scanning electron microscopy, Brunauer Emmett Teller and Barrett Joyner Halenda were carried out for the characterization of the SPs. The bonding rate of the functionalized group (1-acrylamide propyl sulfonic) was calculated to be 2.02 μmol/m2. Positive outcomes were attained for the surface grafting of the SPs. The effect of various chromatographic conditions on the retention time of various analytes was investigated on high performance liquid chromatography. The dual retention mechanism of hydrophilic interaction and ion exchange mechanism of the prepared SPs was confirmed. The polymeric HILIC SPs had more abundant functionalized groups on the surface, which provided superior hydrophilic properties, ion exchange and thus higher selectivity. Compared with the C18 column, the resolution of the HILIC column was better. The HILIC SPs were used for the separation of sulfonamides and flavonoid natural components, and had achieved better baseline separations. In addition, the HILIC mode was used for the separation of the extract of the Fructus Ligustri Lucidi, in which the quality markers had satisfactory peak shape and baseline separation. In conclusion, the prepared surface polymeric SPs were competent for the analysis of polar components and applicable to complex samples.

BushenHuoxue decoction suppresses M1 macrophage polarization and prevents LPS induced inflammatory bone loss by activating AMPK pathway

Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1β (39.42 ± 3.076 ng/L, p < 0.05), IL-6 (49.24 ± 1.766 mg/L, p < 0.05) and TNF-α (286.3 ± 27.12 ng/L, p < 0.05) were significantly increased. The addition of BSHXD decreased the expression levels of IL-1β, IL-6, and TNF-α to 31.55 ± 1.296 ng/L, 37.94 ± 0.8869 mg/L, and 196.4 ± 25.25 ng/L, respectively (p < 0.05). The results of immunofluorescence staining, Western blotting (WB) and flow cytometry indicated that the proportion of M1 macrophages in RAW264.7 cells treated with BSHXD for 24 h was significantly lower than that in the LPS group (13.36% ± 0.9829% VS 24.80% ± 4.619%, p < 0.05). The evidence from in-vitro experiments showed that the immunomodulatory ability of BSHXD may be associated with the activation of AMP-dependent protein kinase (AMPK) pathway in LPS-treated macrophages. In addition, the results of micro-CT, H&E staining, immunohistochemical staining and immunofluorescence staining of mouse skull further demonstrated that BSHXD treatment significantly alleviated LPS-induced local bone loss and inflammatory damage in mouse skull model. All results indicated that BSHXD significantly inhibited inflammatory factors release and M1 polarization of macrophage through AMPK signaling pathway. Therefore, BSHXD may be a promising drug for the treatment of inflammatory bone loss.

Effect of Zhixue Mingmu Formula on Retinal Vasopermeability of Streptozotocin-Induced Diabetic Retinopathy in Rats

Aims: To investigate the efficacy of Zhixue Mingmu Formula (ZXMM), a traditional Chinese herbal compound, for retinal vasopermeability in streptozotocin (STZ)-induced diabetic retinopathy (DR) in rats.&#x0D; Materials and Methods: This experimental study was performed at the Hebei Provincial Key Laboratory of Ophthalmology, Hebei Provincial Eye Hospital within 6 months from January 2021 to June 2021. A total of 70 Sprague-Dawley rats aged 7-8 weeks old and weighing 200-240 g were selected. Animals were categorized into 2 groups:&#x0D; &#x0D; A control group (n = 10): normal rats - receive vehicle.&#x0D; A model group (n = 60): diabetic rats - receive 1% STZ in 0.1 mol/L sodium citrate buffer (45 mg/kg, i.p.).&#x0D; &#x0D; Diabetes was induced via a single intraperitoneal injection of 45 mg/kg STZ. After 72 hours, fasting blood glucose (FBG) levels were measured and FBG ≥16.7 mmol/L was taken as diabetes. After 4 weeks of rearing, 10 normal rats and 50 diabetic rats which were diagnosed with retinopathy by fundus fluorescence angiography were further divided into 6 groups:&#x0D; &#x0D; A normal control group (NG, n=10): normal rats - receive 0.9% normal saline.&#x0D; A model control group (MG, n=10): DR rats - receive 0.9% normal saline.&#x0D; A calcium dobesilate group (CD, n=10): DR rats + calcium dobesilate (135 mg/kg/day, p.o.) daily.&#x0D; A low-dose ZXMM group (LZXMM, n=10): DR rats + low-dose ZXMM (15.3 g/kg/day, p.o.) daily.&#x0D; A moderate-dose ZXMM group (MZXMM, n=10): DR rats + moderate-dose ZXMM (30.6 g/kg/day, p.o.) daily.&#x0D; A high-dose ZXMM group (HZXMM, n=10): DR rats + high-dose ZXMM (45.9 g/kg/day, p.o.) daily.&#x0D; &#x0D; Drug treatments were administered daily for 4 weeks. FBG levels were monitored every 2 weeks. Retinal vasopermeability was measured using an Evans blue assay. Then, serum samples and retinal tissues were harvested to assess the levels of inflammatory factors and the activity of antioxidative enzymes by enzyme-linked immunosorbent assay (ELISA). Retinal hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) protein levels were evaluated by ELISA.&#x0D; Results: In the MG, FBG levels were significantly (P &lt; 0.001) increased, and retinal vasopermeability was markedly (P &lt; 0.001) elevated compared with those in the NG. After oral administration of ZXMM or calcium dobesilate, the elevated retinal vasopermeability was significantly (P &lt; 0.001) decreased in DR rats. Concurrently, ZXMM treatment significantly (P &lt; 0.05) attenuated the levels of the inflammatory factors interleukin-6 (IL-6) and C-reactive protein (CRP) in serum and ameliorated the activity of the antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the retina of DR rats. ZXMM treatment significantly (P &lt; 0.05) decreased HIF-1α and VEGF-A expression in retinal tissues compared with MG treatment. Furthermore, the effects of ZXMM were dose dependent.&#x0D; Conclusion: ZXMM was shown to have a protective effect against retinal vasopermeability in DR comparable to that of calcium dobesilate, and its mechanism may be attributed to inhibition of the downstream pathway of glycaemia-induced hypoxia, inflammation and oxidative stress of retinal tissue.

Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance.

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8+ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.

Screening out anti-inflammatory or anti-viral targets in Xuanfei Baidu Tang through a new technique of reverse finding target

Traditional Chinese herbal compound prescription in Xuanfei Baidu Tang (XBT) has obvious effects in the treatment of COVID-19. However, its effective compounds and targets for the treatment of COVID-19 remain unclear. Computer-Aided Drug Design is used to virtually screen out the anti-inflammatory or anti-viral compounds in XBT, and predict the potential targets by Discovery Studio 2020. Then, we searched for COVID-19 targets using Genecards databases and Protein Data Bank (PDB) databases and compared them to identify targets that were common to both. Finally, the target we screened out is: TP53 (Tumor Protein P53). This article also shows that XBT in the treatment of COVID-19 works in a multi-link and overall synergistic manner. Our results will help to design the new drugs for COVID-19.

Gubenzhike Recipe Ameliorates Respiratory Mucosal Immunity in Mice with Chronic Obstructive Pulmonary Disease through Upregulation of the γδT Lymphocytes and KGF Levels.

Background Gubenzhike recipe, a traditional Chinese herbal compound, was assumed to have a possible beneficial effect on COPD. This study was designed to elucidate the mechanism from the perspective of respiratory mucosal immunity. Methods COPD model was induced by exposure to cigarette smoke and LPS instillation in mice for 12 weeks. Animals were administered solution of Gubenzhike recipe by intragastric gavage daily for 4 weeks. After that, mice were sacrificed for lung function test and histological examination of lung tissues. The levels of IL-6 and IL-13 in serum, bronchoalveolar lavage fluid (BALF), and intestinal mucus were measured by ELISA. The KGF and KGFR in lung tissue were analysed by immunohistochemical staining, ELISA, and western blotting, and the mRNA expressions were assessed by PCR. γδT lymphocytes in the lungs were isolated and analysed by immunohistochemical staining and flow cytometry. Results Gubenzhike recipe improved the structure of airway and damage of lung tissue and also the respiratory status and lung function, reduced the content of IL-6 in serum and BALF and IL-13 in BALF and intestinal mucus, increased the proportion of γδT cells in lung tissue, and promoted the secretion of KGF and KGFR (P < 0.05). Conclusion We for the first time demonstrated an experimental procedure for the isolation of γδT lymphocytes from lung tissue. This study suggested that Gubenzhike recipe could enhance the respiratory mucosal immunity which provided experimental evidence for its effects of reinforcing “wei qi” by means of strengthening vital qi, tonifying spleen and kidney, relieving cough, and reducing phlegm in TCM.

Cognitive enhancement and neuroprotective effects of a traditional Chinese herbal compound medicine on Aβ1-42 induced Alzheimer's disease in rats.

We aimed to explore the role of anovel traditional herbal compound medicine (HCM) in Alzheimer's disease (AD). 72 rats were randomized into control, AD, Donepezil and HCM groups. Injection of -amyloid peptide (A1-42) into the lateral ventricle was used to induce AD in rats. Rats in treatment groups received HCM (1.5, 3.0 and 6.0 g/kg) and Donepezil (0.92 mg/kg) for 21 days, respectively. The spatial learning and memory ability were observed by Morris water maze (MWM) test. Haematoxylin-eosin (HE) staining was carried out for pathological morphology. The contents of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the hippocampus were determined using the spectrophotometric method. A expression was measured by immunohistochemistry and Western blotting. Rats in HCM groups spent less time to locate the platform and performed better in spatial learning and memory than the AD group (p < 0.05). Hippocampus in the HCM (6.0 g/kg) group had acomplete pyramidal cell layer, in which the structure of morphology was normal and the number of neurons was larger than in the AD group (p < 0.01). The contents of SOD, CAT, GSH-Px were notably increased and MDA content was significantly decreased in the hippocampus in HCM groups than in the AD group (p < 0.01). The expression levels of A1-42 in HCM groups were markedly decreased than in the AD group (p < 0.01). HCM has aprotective effect on the learning and memory capacity in AD in rats, indicating that HCM had cognitive enhancing potentials on AD.

Kai Xin San ameliorates scopolamine-induced cognitive dysfunction.

Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

Cardioprotective effects of traditional Chinese medicine Guanmaitong on acute myocardial infarction.

Guanmaitong (GMT) is a traditional Chinese herbal compound that has been used for the treatment of coronary heart disease (CHD) and other cardiovascular diseases. However, the efficacy of GMT in treating cardiovascular diseases remains unclear. The aim of the present study was to investigate the protective mechanisms and identify the targeted proteins and signaling networks associated with the physiological activity of GMT in a rat model of acute myocardial infarction (AMI). Sprague-Dawley rats were randomly allocated into five groups: Control group (sham-operated), the model group, and small, medium, and large dosage GMT groups. The rat model of AMI was established via ligation of the coronary artery. The results indicate that GMT was able to reduce myocardial infarction size and improve the activities of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule 1 (ICAM-1) and interleukin-1. Furthermore, the reduced apoptotic index of the GMT-treated cardiocytes (P<0.05 vs. model group) was in accordance with the downregulated expression of Bax and the upregulated expression of Bcl-2. In conclusion, GMT may exert a protective potential against myocardial infarction injury by inhibiting apoptosis and inflammation of cardiomyocytes, and may offer a promising adjunct treatment for CHD.

Sweet Dream Liquid Chinese Medicine Ameliorates Learning and Memory Deficit in a Rat Model of Paradoxical Sleep Deprivation through the ERK/CREB Signaling Pathway.

Sweet dream oral liquid (SDOL), a traditional Chinese herbal compound contains 17 traditional Chinese medicines. It has various pharmacological effects, such as improving brain dysfunction and increasing sleeping quality. This study investigated the neuroprotective effect and the underlying mechanisms of SDOL-impaired hippocampus learning and memory-induced paradoxical sleep deprivation (PSD) in rats. Sixty Male Wistar rats were randomly divided into six groups. Before PSD, SDOL treatment group rats were intragastrically administered SDOL for 25 days at dose of 2.1, 4.2, and 8.4 mL/kg body weight per day. Normal control group, large platform control group, and PSD groups were treated with normal saline instead of SDOL. After 25 days treatment, PSD and SDOL groups were deprived of paradoxical sleep for 72 h. Then two behavioral studies were conducted to test the spatial learning and memory ability using the open field test and Morris water maze test. Expression of the c-fos, c-jun, cyclic AMP response element binding protein (CREB), extracellular signal-regulated protein kinase (ERK), mitogen-activated protein kinases (MAPK)/ERK kinase (MEK), and p-CREB, p-ERK, and p-MEK in the hippocampus were also assayed by western blot. In this study, PSD decreased the levels of p-CREB, p-ERK, p-MEK, c-fos, and c-jun. However, SDOL treatment increased expressions of these proteins. Our results showed that SDOL improved 72-h PSD-induced cognitive impairment. These affects may be mediated by increasing the contents of c-fos, c-jun, and p-CREB/ERK signaling.

Effect of active fraction of Eriocaulon sieboldianum on human leukemia K562 cells via proliferation inhibition, cell cycle arrest and apoptosis induction.

Eriocaulon sieboldianum (Sieb. & Zucc. ex Steud.), a genus of Eriocaulon in the Eriocaulaceae family, is an edible and medicinal plant used in traditional Chinese medicine. It was processed into healthcare beverages for expelling wind-heat, protecting eyes, and reducing blood fat. Also, it has been used with other herbs as Traditional Chinese herbal compound to treat cancer as adjuvants in tumor therapy in China. However, the active fractions and precise cellular mechanisms of E. sieboldianum extract remain to be illustrated. The goal of this study was to investigate the effects of the active fraction of E. sieboldianum on the growth of K562 cells and understand the possible mechanisms of its action. Our findings suggested that the fraction E3 of E. sieboldianum could effectively inhibit the activity of Aurora kinase and induce apoptosis via blocking cell cycle, up-regulating the expression of proapoptotic proteins including p53 and Bax and reducing the expression of Bcl-2. The levels of Cytochrome C, cleaved caspase-9, cleaved caspase-3 and cleaved PARP were also found to be increased after treatment with fraction E3 of E. sieboldianum. This study could improve the development of E. sieboldianum and raise its application value in cancer adjuvant therapy. Considering it is both a dietary supplement and a traditional Chinese herbal medicine which exhibits anticancer activities, it can be developed into functional food.

Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling.

BackgroundDiabetic nephropathy (DN) is a major cause of chronic kidney failure and characterized by excessive deposition of extracellular matrix. Evidence have shown that transforming growth factor-β1 (TGF-β1) is a key mediator in the development of DN. However, treatment of DN by blocking the TGF-β1/Smad7 pathway remains limited. Xiaokeping mixture (XKP), a traditional Chinese herbal compound, has been used for treatment in patients with DN for many years.MethodsIn the present study, TGF-β1/Smad7 pathway analysis was used to evaluate the therapeutic effect of XKP on DN rats induced by streptozotocin and to address the underlying molecular mechanism. Male rats were divided into four groups: normal control, untreated control group (fed with high fat), irbesartan-treated DN, and XKP-treated DN, respectively. Levels of serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol were detected. Pathological changes of renal tissues were observed by hematoxylin–eosin staining. Immunohistochemical and Western blot analysis were used to detect the expressions of TGF-β1 and Smad7.ResultsThe results demonstrated that XKP can effectively reduce the levels of glucose, serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol. Further studies indicated that inhibition of DN in XKP-treated DN rats was associated with inhibition of TGF-β1/Smad7 signaling as demonstrated by downregulation of TGF-β1 but upregulation of Smad7.ConclusionThe data obtained from the present study indicate that XKP may be a therapeutic agent for DN.

Tripchlorolide improves cognitive deficits by reducing amyloid β and upregulating synapse-related proteins in a transgenic model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by early impairments in memory and progressive neurodegeneration. Disruption of synaptic plasticity processes that underlie learning and memory contribute partly to this pathophysiology. Tripchlorolide (T4 ), an extract from a traditional Chinese herbal Tripterygium wilfordii Hook F, has been shown to be neuroprotective in animal models of Parkinson's disease and to improve cognitive deficits in senescence-accelerated mouse P8. In this study, we investigated the effect of T4 on cognitive decline and synaptic plasticity in five times familial AD (5XFAD) mice co-expressing mutated amyloid precursor protein and presenilin-1. Five-month-old 5XFAD mice and wild type littermates were intraperitoneally injected with T4 , 5 μg/kg or 25 μg/kg, every other day for 60 days. T4 treatment significantly improved spatial learning and memory, alleviated synaptic ultrastructure degradation, up-regulated expression of synapse-related proteins, including synaptophysin, post-synaptic density-95, N-methyl-D-aspartate receptor subunit 1, phosphorylation of calcium/calmodulin dependent protein kinase II α, and phosphorylation of cyclic AMP-response element binding protein, and promoted activation of the phophoinositide-3-kinase-Akt-mammalian target of rapamycin signaling pathway in 5XFAD mice. Accumulation of amyloid β (Aβ) may contribute to synapse dysfunction and memory impairment in AD. We found that T4 treatment significantly reduced cerebral Aβ deposits and lowered Aβ levels in brain homogenates. These effects coincided with a reduction in cleavage of β-carboxyl-terminal amyloid precursor protein (APP) fragment, levels of soluble APPβ, and protein expression of β-site APP cleaving enzyme 1. Taken together, our findings identify T4 as a potent negative regulator of brain Aβ levels and show that it significantly ameliorates synaptic degeneration and cognitive deficits in a mouse model of AD.