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Evidence-based complementary and alternative medicine
Oxford University Press
Evidence-based complementary and alternative medicine

Oxford University Press

1741-427X

Evidence-based complementary and alternative medicine/Journal Evidence-based complementary and alternative medicineSCIAHCI
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    Evaluation of Subchronic Toxicity and Genotoxicity of Ethanolic Extract of Aster glehni Leaves and Stems

    Mi Kyung LimJu Yeon KimJeongho JeongEun Hye Han...
    11页
    查看更多>>摘要:Aster glehni, a traditional plant on Ulleung Island in the Republic of Korea, has been recognized for its multiple medicinal properties. However, potential toxicity and safety analyses of A. glehni have not been previously investigated. Therefore, this study aimed to evaluate the safety profile of ethanolic extract of A. glehni leaves and stems (EAG) in terms of genotoxicity and subchronic oral animal toxicity under OECD guidelines and GLP conditions. Toxicological assessments were performed at doses of 1,250, 2,500, and 5,000 mg/kg/day in a 13-week oral repeated-dose toxicity study of EAG in male and female SD rats. In addition, an Ames test, an in vitro mammalian chromosomal aberration test, and a micronucleus test were performed. No toxicological changes in clinical signs, body weights, water and food consumption, urinalysis, hematology, clinical biochemistry, gross findings, and histopathological examinations were observed in subchronic oral animal toxicity. In addition, EAG gave negative results when evaluated using in vitro and in vivo genotoxicity tests. In conclusion, the no-observed-adverse-effect level (NOAEL) of EAG was considered to be 5,000 mg/kg/day, and no target organs were identified in both sexes of rats. EAG was also classified as nonmutagenic and nonclastogenic in genotoxicity testing. Collectively, these results show a lack of general toxicity and genotoxicity for EAG that supports clinical work for development as a herbal medicine.

    Processing and Compatibility of Corydalis yanhusuo: Phytochemistry, Pharmacology, Pharmacokinetics, and Safety

    Lingyan WuYangYangZhujun MaoJianjun Wu...
    9页
    查看更多>>摘要:Processed and polyherbal formulations (compatibility) are widely used in traditional Chinese medicine (TCM). However, processing and compatibility may alter the efficacy and safety of herbal medicines, and therefore, evaluating the herbal medicines changes after processing and compatibility is important for their safety. Since Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T.Wang ex Z.Y.Su & C.Y.Wu (Family: Papaveraceae and Genera: Corydalis), a traditional medicinal plant in China, Japan, Korea, and other Asian countries, has been used for treating a wide range of medical conditions, it is an ideal representative of studying the effects of processing and compatibility on efficacy and toxicity. In this paper, information was obtained by searching electronic databases, classic books, PhD and MSc dissertations, local conference papers, and unpublished materials prior to July 2021. We provide a summary of the phytochemistry, pharmacology, pharmacokinetics, quality control, and safety of C. yanhusuo under various processing or compatibility conditions. Based on our findings, vinegar processing is probably the best C. yanhusuo processing method, which could increase the absorption rate of tetrahydropalmatine (THP) in the heart, liver, spleen, lung, and brain tissues and alleviate mice muscle tremors and liver damage caused by C. yanhusuo. These results indicate that processing and compatibility can reduce toxicity and increase the efficacy of C. yanhusuo. The information provides an expanded understanding of the efficacy and toxicity mechanisms of TCM compounds, which is valuable for industrial production quality control and future drug research.

    Identification of Chemical Components of Qi-Fu-Yin and Its Prototype Components and Metabolites in Rat Plasma and Cerebrospinal Fluid via UPLC-Q-TOF-MS

    Hengyu LiHongwei ZhaoYong YangDongmei Qi...
    27页
    查看更多>>摘要:Qi-Fu-Yin, a traditional Chinese medicine formula, has been used to treat Alzheimer's disease (AD, a neurodegenerative disorder) in clinical setting. In this study, the chemical components of Qi-Fu-Yin and its prototype components and metabolites in rat plasma and cerebrospinal fluid, after oral administration, were preliminarily characterized via ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). A total of 180 compounds, including saponins, flavonoids, organic acids, sucrose esters, oligosaccharide esters, phthalides, phenylethanoid glycosides, alkaloids, xanthones, terpene lactones, ionones, and iridoid glycoside, were tentatively characterized. For the first time, 51 prototypical components and 26 metabolites, including saponins, phthalides, flavonoids, sucrose esters, organic acids, alkaloids, ionones, terpene lactones, iridoid glycoside, and their derivatives, have been tentatively identified in the plasma. Furthermore, 10 prototypical components (including butylidenephthalide, butylphthalide, 20(S)-ginsenoside Rh_1 20(R)-gin-senoside Rh_1 and zingibroside R_1) and 6 metabolites were preliminarily characterized in cerebrospinal fluid. These results were beneficial to the discovery of the active components of Qi-Fu-Yin anti-AD.

    Identification of Potential Biomarkers of Depression and Network Pharmacology Approach to Investigate the Mechanism of Key Genes and Therapeutic Traditional Chinese Medicine in the Treatment of Depression

    Yucong ShiDan ChenShengsuo MaHuachong Xu...
    14页
    查看更多>>摘要:Background. To explore the potential target of depression and the mechanism of related traditional Chinese medicine in the treatment of depression. Method. Differential gene expression in depression patients and controls was analyzed in the GEO database. Key genes for depression were obtained by searching the disease databases. The COREMINE Medical database was used to search for Chinese medicines corresponding to the key genes in the treatment of depression, and the network pharmacological analysis was performed on these Chinese medicines. Then, protein-protein interaction analysis was conducted. Prediction of gene phenotypes was based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment scores. Results. The total number of differentially expressed genes in the GEO database was 147. Combined with the GEO dataset and disease database, a total of 3533 depression-related genes were analyzed. After screening in COREMINE Medical, it was found that the top 4 traditional Chinese medicines with the highest frequency for depression were Paeonia lactiflora Pall., Crocus sativus L, Bupleurum chinense DC, and Cannabis sativa L. The compound target network consisted of 24 compounds and 138 corresponding targets, and the key targets involved PRKACA, NCOA2, PPARA, and so on. GO and KEGG analysis revealed that the most commonly used Chinese medicine could regulate multiple aspects of depression through these targets, related to metabolism, neuroendocrine function, and neuroimmunity. Prediction and analysis of protein-protein interactions resulted in the selection of nine hub genes (ESR1, HSP90AA1, JUN, MAPK1, MAPK14, MAPK8, RBI, RELA, and TP53). In addition, a total of four ingredients (petunidin, isorhamnetin, quercetin, and luteolin) from this Chinese medicine could act on these hub genes. Conclusions. Our research revealed the complicated antidepressant mechanism of the most commonly used Chinese medicines and also provided a rational strategy for revealing the complex composition and function of Chinese herbal formulas.

    Huanglian Jiedu Decoction Exerts Antipyretic Effect by Inhibiting MAPK Signaling Pathway

    Honghong LiuShengqi NiuYuling TongLisheng Chen...
    13页
    查看更多>>摘要:Aim. The aim of this study was to explore the antipyretic effect and potential mechanism of Huanglian Jiedu Decoction (HLJDD) on LPS-induced fever in rats. Materials and Methods. The fever rat model was established by LPS. Anal temperature of rats was measured every 1 hour after modeling. TNF-α, IL-6, PGE_2, and cAMP in rat serum or hypothalamus tissue were detected by ELISA kit. In order to explore the potential active ingredients and mechanism of antipyretic effect of HLJDD, we predicted the underlying antipyretic mechanism by using network pharmacology and then verified its mechanism by Western Blotting. Results. The results showed that HLJDD can alleviate LPS-induced fever in rats. The expression levels of TNF-α, IL-6, PGE_2, and cAMP in the treatment group were significantly lower than those in the model group. Western Blotting results showed that the protein expression of p-ERK, p-JNK, and p-P38 was significantly inhibited. Conclusion. The findings suggest that HLJDD has a good antipyretic effect on LPS-induced fever in rats, which may be closely related to the inhibition of MAPK signaling pathway.

    Inhibitory Effects of Inonotus obliquus Polysaccharide on Inflammatory Response in Toxoplasma gondii-Infected RAW264.7 Macrophages

    Wei WangXuemei ZhangKexin YanHongyuan Zhou...
    11页
    查看更多>>摘要:Our previous reports have shown that Inonotus obliquus polysaccharide (IOP) has protective effects against Toxoplasma gondii (T. gondii) infection in vivo. The aim of the present research is to explore the in vitro anti-inflammatory effects of IOP and its mechanism in RAW264.7 macrophages infected by T. gondii. In this study, it is indicated that IOP decreased the excessive secretion of inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-4, and IL-6 in T. gondii-inkcted RAW264.7 macrophages. IOP effectively suppressed the mRNA expression of these cytokines and che-mokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-la (MIP-1α). Moreover, IOP inhibited the phosphorylation of inhibitor kappa B kinase α/β (IKKα/β), inhibitor κBα (IκBα:), p65 in nuclear factor-kappa B (NF-κB) signaling pathway and p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) in mitogen-activated protein kinases (MAPKs) signaling pathway. Meantime, IOP prevented NF-κB p65 and c-Jun translocation from the cytoplasm to the nucleus. Further, IOP downregulated the protein expression of toll-like receptor 2 (TLR2) and TLR4 in T. gondii-infected RAW264.7 macrophages. The above results suggest that IOP can inhibit the inflammatory response infected with T. gondii via regulating TLR2/TLR4-NF-κB/MAPKs pathways and exerting its anti-T. gondii role in vitro.

    Acupuncture Delays Cartilage Degeneration through Upregulating SIRT1 Expression in Rats with Osteoarthritis

    Hui LiuTingting ZhangMin LiuChunhong Wang...
    11页
    查看更多>>摘要:Silent mating type information regulation 2 homolog 1 (SIRT1) has been reported to inhibit osteoarthritic gene expression in chondrocytes. Here, efforts in this study were made to unveil the specific role of SIRT1 in the therapy of acupuncture on cartilage degeneration in osteoarthritis (OA). Specifically, OA was established by the anterior cruciate ligament transection method in the right knee joint of rats, subsequent to which acupuncture was performed on two acupoints. Injection with shSIRT1 sequence-inserted lentiviruses was conducted to investigate the role of SIRT1 in acupuncture-mediated OA. Morphological changes and cell apoptosis in rat OA cartilages were examined by safranin-O staining and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay, respectively. The serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-2 in OA rats were assessed by enzyme-linked immunosorbent assay (ELISA). The expressions of SIRT1, cartilage matrix degradation-related proteins (matrix metalloproteinase (MMP)-9 and ADAMTS5), NF-κB signaling-related markers (p-p65/p65 and p-IκBα/ IκBα), and cartilage matrix synthesis-related proteins (collagen II and aggrecan) in the OA cartilage were analyzed by western blot. As a result, acupuncture counteracted OA-associated upregulation of TNF-α, IL-2, cartilage matrix degradation-related proteins, and NF-κB signaling-related markers, morphological damage, apoptosis, SIRT1 downregulation, and loss of cartilage matrix synthesis-related proteins in rat articular cartilages. SIRT1 silencing reversed acupuncture-induced counteractive effects on the aforementioned OA-associated phenomena (except apoptosis, the experiment regarding which under SIRT1 silencing was not performed). Collectively, acupuncture inhibited chondrocyte apoptosis, inflammation, NF-κB signaling activation, and cartilage matrix degradation by upregulating SIRT1 expression to delay OA-associated cartilage degeneration.

    Exploring the Potential Mechanism of Chuanxiong Rhizoma Treatment for Migraine Based on Systems Pharmacology

    Feipeng GongWenting WuHengli TongQianfeng Gong...
    15页
    查看更多>>摘要:Migraine is a disease whose aetiology and mechanism are not yet clear. Chuanxiong Rhizoma (CR) is employed in traditional Chinese medicine (TCM) to treat various disorders. CR is effective for migraine, but its active compounds, drug targets, and exact molecular mechanism remain unclear. In this study, we used the method of systems pharmacology to address the above issues. We first established the drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network related to the treatment of migraine with CR and then established gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results suggest that the treatment process may be related to the regulation of inflammation and neural activity. The docking results also revealed that PTGS2 and TRPV1 could directly bind to the active compounds that could regulate them. In addition, we found that CR affected 11 targets that were more highly expressed in the liver or heart but were the lowest in the whole brain. It also expounds the description of CR channel tropism in TCM theory from these angles. These findings not only indicate that CR can be developed as a potential effective drug for the treatment of migraine but also demonstrate the application of systems pharmacology in the discovery of herbal-based disease therapies.

    TLC-Based Metabolite Profiling and Bioactivity-Based Scientific Validation for Use of Water Extracts in AYUSH Formulations

    Sultan ZahiruddinAbida ParveenWashim KhanRabea Parveen...
    12页
    查看更多>>摘要:We aimed to develop a chromatographic method for scientific validation of water extract of some important Indian traditional plants used in AYUSH-based formulation as immunomodulator and to evaluate their bioactive potential. Fruits of Phyllanthus emblica L. and Piper nigrum L, stem of Tinospora cordifolia (Willd.) Miers, rhizome of Curcuma longa L, leaves of Ocimum sanctum L. and Achillea millefolium L, roots of Withania somnifera L, and stem bark of Azadirachta indica A. Juss. were coarsely powdered and extracted in three different solvents (water, ethanol, and hydroethanol). The antioxidant potential was determined through 1, 1-diphenyl-2-picrylhydrazyl and ferric reducing capacity methods. Thin-layer chromatography (TLC) was carried out for the comparative metabolite profiling of the extracts using toluene, ethyl acetate, and formic acid (5:4:1, v/v/v) as a solvent system. In vitro immunomodulatory activity of the extracts has been tested on splenocyte proliferation and pinocytic assay. Hydroethanolic extract (HEE) of most of the plant materials has the highest phenolic and flavonoid contents, followed by water extract (WE) and ethanolic extract (EE), whereas the water extracts of most of the plant material showed better antioxidant activity. Almost all extract exhibited splenocyte proliferation and pinocytic activity in a dose-dependent manner. But water extract showed significantly higher splenocyte proliferation and pinocytic activity as compared to the other two extracts. TLC analysis resulted in detection of totally 63 and 56 metabolites at 254 nm and 366 nm, respectively. Through principal component analysis (PCA), it was observed that metabolite pattern of different extracts from same plant materials may be different or similar. This preliminary result can be used for quality evaluation and to develop a synergy-based polyherbal combination of water extracts of selected plant materials.

    Effect of Yoganidra on Blood Pressure, Hs-CRP, and Lipid Profile of Hypertensive Subjects: A Pilot Study

    J. P. DevrajB. Santosh KumarM. Raja SriswanB. Jagdish...
    9页
    查看更多>>摘要:Background. Yoganidra is a systematic method of promoting a state of complete physical, mental, and emotional relaxation. It is a safe, inexpensive, and very effective method of management of hypertension when used along with standard pharmacological therapy. This study aims to assess the effect of yoganidra on blood pressure (both systolic blood pressure (SBP) and diastolic blood pressure (DBP)), Hs-CRP, and lipid profile of hypertensive subjects at the time of enrollment (subjects that are hypertensive at the time of enrollment). Methods. Both treated and untreated subjects (n = 74) with hypertension (blood pressure >140/90 mmHg) and age between 35 and 70 years were included in this study after obtaining ICMR-NIN-IEC approval and written informed consent from all subjects. Subjects with critical illness and/or psychological disturbances were excluded from this study. The subjects in the experimental group (n = 31) practiced yoganidra for 45 minutes daily for 12 weeks under strict supervision. There was no intervention in the control group (n = 43). Weekly blood pressure was recorded in the experimental group, whereas it was performed at baseline and at endpoint for control groups. Hs-CRP and lipid profile were estimated at baseline and endpoint for both the groups. Results. A significant reduction in mean SBP from 142.9 mm Hg (SD± 16.46) to 118.68 mm Hg (SD±9.21; p value 0.0001) and DBP from 89.84 mm Hg (SD ± 10.42) to 77.03 mm Hg (SD ± 6.47: p value 0.0001) was observed among the experimental group after 12 weeks of yoganidra practice when compared with the control group. A significant reduction in mean Hs-CRP (2.21 ± 1.49 to 1.06 ± 0.82 mg/L, p < 0.001***) was observed among the experimental group. There were no significant differences between triglycerides and total cholesterol levels, whereas LDL-C and HDL-C showed a trend of improvement in the experimental group after intervention. Conclusions. In this pilot study, we observed a significant reduction in blood pressure and Hs-CRP in the yoganidra group compared with the control group. There were no significant side effects observed in the intervention group during the study period.