BMC Complementary Medicine and Therapies

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The effect of bovine milk lactoferrin-loaded exosomes (exoLF) on human MDA-MB-231 breast cancer cell line
BMC Complementary Medicine and Therapies - Tập 23 - Trang 1-10 - 2023
Reihaneh Ramezani, Mozhdeh Mohammadian, Elaheh Sadat Hosseini, Mehrak Zare
Cancer is still the most challenging disease and is responsible for many deaths worldwide. Considerable research now focuses on targeted therapy in cancer using natural components to improve anti-tumor efficacy and reduce unfavorable effects. Lactoferrin is an iron-binding glycoprotein found in body fluids. Increasing evidence suggests that lactoferrin is a safe agent capable of inducing anti-cancer effects. Therefore, we conducted a study to evaluate the effects of the exosomal form of bovine milk lactoferrin on a human MDA-MB-231 breast cancer cell line. The exosomes were isolated from cancer cells by ultracentrifugation and incorporated with bovine milk lactoferrin through the incubation method. The average size of the purified exosome was determined using SEM imaging and DLS analysis. The maximum percentage of lactoferrin-loaded exosomes (exoLF) was achieved by incubating 1 mg/ml of lactoferrin with 30 µg/ml of MDA-MB-231 cells-derived exosomes. Following treatment of MDA-MB-231 cancer cells and normal cells with 1 mg/ml exoLF MTT assay applied to evaluate the cytotoxicity, PI/ annexin V analysis was carried out to illustrate the apoptotic phenotype, and the real-time PCR was performed to assess the pro-apoptotic protein, Bid, and anti-apoptotic protein, Bcl-2. The average size of the purified exosome was about 100 nm. The maximum lactoferrin loading efficiency of exoLF was 29.72%. MTT assay showed that although the 1 mg/ml exoLF treatment of MDA-MB-231 cancer cells induced 50% cell growth inhibition, normal mesenchymal stem cells remained viable. PI/ annexin V analysis revealed that 34% of cancer cells had late apoptotic phenotype after treatment. The real-time PCR showed an elevated expression of pro-apoptotic protein Bid and diminished anti-apoptotic protein Bcl-2 following exoLF treatment. These results suggested that exoLF could induce selective cytotoxicity against cancer cells compared to normal cells. Incorporating lactoferrin into the exosome seems an effective agent for cancer therapy. However, further studies are required to evaluate anti-tumor efficacy and the underlying mechanism of exoLF in various cancer cell lines and animal models.
Pao Pereira extract suppresses benign prostatic hyperplasia by inhibiting inflammation-associated NFκB signaling
BMC Complementary Medicine and Therapies - - 2020
Yunsheng Dong, Jiakuan Liu, Zhaoli Xue, Jingya Sun, Zhengnan Huang, Yifeng Jing, Bangmin Han, Bing Shen, Jun Yan, Ruimin Huang
Abstract Background

Our previous study revealed the extract from the bark of an Amazonian tree Pao Pereira can suppress benign prostatic hyperplasia (BPH) in a rat model. Herein, we examined its inhibitory effects on human BPH cells and dissect its molecular mechanism.

Methods

We applied Pao extract to human BPH epithelial BPH-1 and prostate myofibroblast WPMY-1 cells. Cell viability, apoptosis and immunoblotting were performed, followed by gene expression profiling and gene set enrichment analysis (GSEA) to detect the differentially expressed genes and signaling pathway induced by Pao extract. Human ex vivo BPH explant organ culture was also used to examine the effects of Pao extract on human BPH tissues.

Results

Pao extract treatment inhibited viability and induced apoptosis in human BPH-1 and WPMY-1 cells. Gene expression profiling and the following validation indicated that the expression levels of pro-apoptotic genes (eg. PCDC4, CHOP and FBXO32) were induced by Pao extract in both two cell lines. GSEA further revealed that Pao extract treatment was negatively associated with the activation of NFκB signaling. Pao extract suppressed the transcriptional activity of NFκB and down-regulated its target genes involved in inflammation (CXCL5, CXCL6 and CXCL12) and extracellular matrix (ECM) remodeling (HAS2, TNC and MMP13) in both cultured cells and human ex vivo BPH explants.

Conclusion

In both BPH epithelial and stromal cells, Pao extract induces apoptosis by upregulating the pro-apoptotic genes and inhibiting the inflammation-associated NFκB signaling via reducing phosphorylation of NFκB subunit RelA. Our data suggest that Pao extract may be a promising phytotherapeutic agent for BPH.

Utilisation of traditional medicine among women diagnosed with breast cancer in Ghana: a descriptive phenomenological study
BMC Complementary Medicine and Therapies - Tập 24 - Trang 1-11 - 2024
Adwoa Bemah Boamah Mensah, Stella Baffour Asuo, Kofi Boamah Mensah, Joshua Okyere, Shalini Kulasingam, Beth Virnig, Joe-Nat Clegg-Lamptey
Women living with breast cancer (BC) rely on traditional medicine (TM) in addition to orthodox medicine. There is a need to understand how and why women diagnosed with BC utilise TM. This study explored and described the lived experiences of women living with BC in terms of their utilisation of traditional medicine. A descriptive phenomenology design was used to purposively conduct 20 face-to-face in-depth interviews using a semi-structured interview guide. Data were analysed using NVivo-12 based on Collaizzi’s framework for thematic data analysis. Overall, five main themes emerged, namely: sources of knowledge on TM, motivations for using TM, treatment modalities, timing for the initiation of TM, the reasons for discontinuing use of TM, and the decision to seek orthodox medicine. Under the category of motivations for using TM, four themes emerged: financial difficulties and perceived cost effectiveness of TM, influence of social networks, including family and friends, assurance of non-invasive treatment, delays at the healthcare facility, and side effects of orthodox treatment. Non-invasive treatments included herbal concoctions, natural food consumption, and skin application treatments. Regarding the timing of initiation, TM was used in the initial stage of symptom recognition prior to the decision to seek orthodox medicine, and was also used complementarily or as an alternative after seeking orthodox medicine. However, patients eventually stopped using TM due to the persistence of symptoms and the progression of cancer to a more advanced stage, and disapproval by orthodox practitioners. Women living with BC in Ghana utilise traditional medicine (TM) for many reasons and report their family, friends and the media as a main source of information. A combination of herbal concoctions and skin application modalities is obtained from TM practitioners to treat their BC. However, they eventually discontinue TM when symptoms persist or when disapproval is expressed by their orthodox healthcare providers. We conclude that there is an opportunity to better integrate TM into the standard of oncological care for BC patients.
The prevalence of complementary and alternative medicine use in the general population of Babol, North of Iran, 2018
BMC Complementary Medicine and Therapies - Tập 21 - Trang 1-12 - 2021
Reihaneh Moeini, Seyyed Ali Mozaffarpur, Morteza Mojahedi, Seyed Davoud Nasrolahpour Shirvani, Narjes Gorji, Roshanak Saghebi, Farid Abolhassani Shahreza, Hoda Shirafkan
Complementary and Alternative Medicine (CAM) have recently become more popular and accepted worldwide. One principal step to identify the status and organize strategies of CAM is evaluating the manner and the prevalence of its usage among people. This study aimed to investigate the prevalence of CAM modalities usage by the people of Babol, a central city in the North of Iran, in 2018. Using the original International CAM Questionnaire (I-CAM-Q), a questionnaire was redesigned in Persian (Farsi) with some changes such as adding special modalities in Iran and its validity and reliability were assessed. Six hundred households were evaluated using a cluster sampling method in 2018 spring by 12 trained interviewers. Finally, 1770 questionnaires were correctly completed. A total of 110 participants (6.21% of the completed questionnaires) had visited CAM therapists in the last year, 109 persons (6.15%) had received prescriptions from physicians and paramedics to use CAM, and a total of 1032 people (58.30%) used herbs and herbal medicines in the last 12 months. Also, 1265 individuals (71.46%) had used CAM throughout their lives. The most popular methods were herbal medicine (65.76%), Persian Medicine (13.78%), water therapy (10.45%) and music therapy (8.36%). The use of CAM was more popular among women. The general use of CAM in Babol was similar to other studies, but there were fewer visits by CAM therapists and less frequent adoption of common methods including homeopathy, acupuncture, and energy therapy. It was found that CAM was mostly used for non-serious diseases such as cold and transient gastrointestinal disorders, a pattern that is different from other studies in this field.
Correction: Effects of Vitellaria paradoxa (C.F. Gaertn.) Aqueous leaf extract administration on Salmonella typhimurium-infected rats
BMC Complementary Medicine and Therapies - Tập 23 - Trang 1-1 - 2023
Siméon Pierre Chegaing Fodouop, Sedric Donald Tala, Lunga Paul Keilah, Norbert Kodjio, Mefokou Didiane Yemele, Armel Herve Nwabo Kamdje, Bridget Nji-kah, Joseph Tchoumboue, Donatien Gatsing
A randomized, double-blind, placebo-controlled crossover clinical trial to evaluate the anti-diabetic effects of Allium hookeri extract in the subjects with prediabetes
BMC Complementary Medicine and Therapies - Tập 20 - Trang 1-8 - 2020
Soo-Hyun Park, Ui-Jin Bae, Eun-Kyung Choi, Su-Jin Jung, Sung-Hyen Lee, Jae-Heon Yang, You-Suk Kim, Do-Youn Jeong, Hyun-Ju Kim, Byung-Hyun Park, Soo-Wan Chae
Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects. Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value < 0.05 was considered statistically significant. Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed. The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control. The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).
6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions
BMC Complementary Medicine and Therapies - Tập 20 - Trang 1-10 - 2020
Marta Woźniak, Sebastian Makuch, Kinga Winograd, Jerzy Wiśniewski, Piotr Ziółkowski, Siddarth Agrawal
The development and growth of colorectal cancer based on constitutive activation of numerous signaling pathways that stimulate proliferation and metastasis. Plant-derived agents excel by targeting multiple aspects of tumor progression. Previous investigations have shown that ginger derivatives- shogaols possess anti-cancer and anti-inflammatory effects. In the present study, we have examined the anti-cancer effects of 6-shogaol alongside with the most widely used chemotherapeutic agents/regimens in the tumor-like microenvironment conditions. Cytotoxicity on two colon cancer cell lines (SW480 and SW620) was measured by MTT test. Apoptosisassay, immunocytochemical and Western blotting analysis for autophagy and apoptosis detection were performed. Here, we report that 6-shogaol by itself or in combination with chemotherapeutic agents/regimens exerted a cytotoxic effect on CRC cells. Cell death might be linked with the activation of autophagy and apoptosis-related pathways. In the tumor-like microenvironment, which is characterized by hypoxia and glucose starvation, 6-shogaol with chemotherapeutics is significantly more potent than conventional chemotherapy alone. Collectively, our data suggest that the addition of 6-shogaol to established chemotherapeutic regimens could potentially be a remarkable therapeutic strategy for colorectal cancer.
Molecular mechanism of resveratrol promoting differentiation of preosteoblastic MC3T3-E1 cells based on network pharmacology and experimental validation
BMC Complementary Medicine and Therapies - Tập 24 Số 1
Ya‐Ling He, Fei Liu, Mengqi He, Fayu Long, Hu Ding, Jingwen Chen, Fei Miao, Zhenlong Wang
Abstract

The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.

Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-κB pathway
BMC Complementary Medicine and Therapies - Tập 22 - Trang 1-17 - 2022
Nida Baig, Rabia Sultan, Shamim Akhtar Qureshi
Type 2 diabetes mellitus (T2DM) approximately constitutes 90% of the reported cases. 30-40% of diabetics eventually develop diabetic nephropathy (DN); accounting for one of the major causes of morbidity and mortality. Increased glucose autoxidation and non-enzymatic glycation of proteins in diabetic kidneys lead to the excessive generation of reactive oxygen species (ROS) that results in lipid peroxidation and activation of inflammatory mediators which overwhelms the scavenging capacity of the antioxidant defense system (Nrf2/Keap1/HO-1). Centratherum anthelminticum commonly called as kali zeeri (bitter cumin) and its seeds are well known for culinary purposes in Asia (Pakistan). It has reported anti-inflammatory, antioxidant, and anti-diabetic activities. The present study has attempted to explore the in-vivo anti-inflammatory, antioxidant and antihyperglycemic potential of the C. anthelminticum seed’s fixed oil (FO) and its fractions in high fat-high fructose-streptozotocin (HF-HFr-STZ) induced T2DM rat model. The T2DM rat model was developed by giving a high-fat and high-fructose diet followed by a single intraperitoneal injection of streptozotocin (STZ 60 mg/kg) on 28th day of the trial. After 72 hours of this injection, rats showing fasting blood glucose (FBG) levels≥230 mg/dL were recruited into six groups. These groups were orally administered distilled water (1 mL/kg), Gliclazide (200 mg/kg), Centratherum anthelminticum seed (FO) and its hexane (HF), chloroform (CF) and ethanol (EF) soluble fractions (200 mg/kg each), respectively for 4 weeks (i.e. 28 days). Blood, serum, and kidney tissue samples of euthanized animals were used for biochemical, pro-inflammatory, and antioxidant markers (ELISA, qRT-PCR, and spectrophotometric assays) and histology, respectively. C. anthelminticum FO and its fractions reduced the lipid peroxidation, and improved the antioxidant parameters: enzymatic (SOD, CAT, and GPx), non-enzymatic (GSH), and mRNA expression of anti-inflammatory markers (Nrf-2, keap1, and HO-1). mRNA expression of inflammatory and apoptotic markers (TNF-α, IL-1β, COX-1, NF-κB, Bax, and Bcl-2) were attenuated along with improved kidney architecture. C. anthelminticum can mitigate inflammation and oxidative stress in early DN. The anti-nephropathic effect can be attributed to its ability to down-regulate NF-κB and by bringing the Nrf-2 expression levels to near normal.
Effects of Si-Miao-Yong-An decoction on myocardial I/R rats by regulating gut microbiota to inhibit LPS-induced TLR4/NF-κB signaling pathway
BMC Complementary Medicine and Therapies - Tập 23 - Trang 1-16 - 2023
Yuting Cui, Fangyuan Zhang, Weiming Xu, Ziyun Li, Jiaxi Zou, Ping Gao, Jingqing Hu
Coronary Artery Disease (CAD) is primarily caused by inflammation which is closely linked to the gut microbiota. Si-Miao-Yong-An (SMYA) decoction is a traditional Chinese herbal formula with anti-inflammatory properties that found to be effective against CAD. However, it is still unclear whether SMYA can modulate gut microbiota and whether it contributes to the improvement of CAD by reducing inflammation and regulating the gut microbiota. The identification of components in the SMYA extract was conducted using the HPLC method. A total of four groups of SD rats were orally administered with SMYA for 28 days. The levels of inflammatory biomarkers and myocardial damage biomarkers were measured through ELISA, while echocardiography was used to assess heart function. Histological alterations in the myocardial and colonic tissues were examined following H&E staining. Western blotting was performed to evaluate protein expression, whereas alterations in gut microbiota were determined by 16 s rDNA sequencing. SMYA was found to enhance cardiac function and decrease the expression of serum CK-MB and LDH. SMYA was also observed to inhibit the TLR4/NF-κB signaling pathway by downregulating the protein expression of myocardial TLR4, MyD88, and p-P65, leading to a reduction in serum pro-inflammatory factors. SMYA modified the composition of gut microbiota by decreasing the Firmicutes/Bacteroidetes ratio, modulating Prevotellaceae_Ga6A1 and Prevotellaceae_NK3B3 linked to the LPS/TLR4/NF-κB pathway, and increasing beneficial microbiota such as Bacteroidetes, Alloprevotella, and other bacterial species. Moreover, SMYA was found to safeguard the intestinal mucosal and villi structures, elevate the expression of tight junction protein (ZO-1, occludin), and reduce intestinal permeability and inflammation. The results indicate that SMYA has the potential to modulate the gut microbiota and protect the intestinal barrier, thereby reducing the translocation of LPS into circulation. SMYA was also found to inhibit the LPS-induced TLR4/NF-κB signaling pathway, leading to a decrease in the release of inflammatory factors, which ultimately mitigated myocardial injury. Hence, SMYA holds promise as a therapeutic agent for the management of CAD.
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