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Fitoterapia Jul 2023Oxymatrine (OMT), was identified as a quinolizidine alkaloid, which was one of the major matrine-type alkaloids extracted from Sophora medicinal plants. Growing studies... (Review)
Review
Oxymatrine (OMT), was identified as a quinolizidine alkaloid, which was one of the major matrine-type alkaloids extracted from Sophora medicinal plants. Growing studies revealed that OMT has a wide range of beneficial pharmacological values, consisting of anticancer, antidiabetic, antivirus, and antiinflammtion, as well as the protective activities to the brain, liver, heart, lung, vascular, gastrointestinal, bone, kidney, and skin organs. Various in vitro and in vivo models of pharmacological actions were recorded in regard to the usage of alkaloidal OMT. Mechanisms underlying anticancer activity of this compound may have been possibly involved anti-proliferation, invasion, migration, angiogenesis, epithelial-mesenchymal transition of cells, autophagy, especially apoptotic cell deaths. OMT could reduce hyperglycemia and hyperlipemia in a high-fat diet and streptozotocin-stimulated diabetic mice by improving insulin secretion and sensitivity. OMT suppressed gastric ulcer via gastric inflammatory and oxidative inhibitions, and pro-apoptotic actions. It turns out that OMT is relatively safe for cell and animal experiments. In this study, we offer a systematic review of natural occurrence, pharmacological potentials, possible mechanisms of action, pharmacokinetics, and bioavailability. Clinical research with OMT is needed to extensively elucidate its health potential benefits.
Topics: Mice; Animals; Diabetes Mellitus, Experimental; Molecular Structure; Alkaloids; Matrines; Quinolizines
PubMed: 37295753
DOI: 10.1016/j.fitote.2023.105565 -
Journal of Evidence-based Complementary... Apr 2016Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal... (Review)
Review
Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal plants in Iran with already investigated anticancer effects on various cell lines. Thirty-six medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plants' anticancer effect were introduced. Phenolic and alkaloid compounds were demonstrated to have anticancer effects on various cancers in most studies. The plants and their active compounds exerted anticancer effects by removing free radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and inhibition of angiogenesis. The investigated plants in Iran contain the compounds that are able to contribute effectively to fighting cancer cells. Therefore, the extract and active compounds of the medicinal plants introduced in this review article could open a way to conduct clinical trials on cancer and greatly help researchers and pharmacists develop new anticancer drugs.
Topics: Animals; Antineoplastic Agents; Cell Line; Cell Survival; Humans; Iran; Mice; Plant Extracts; Plants, Medicinal
PubMed: 26297173
DOI: 10.1177/2156587215600873 -
International Journal of Biological... Mar 2023Despite advances in treating patients with melanoma, there are still many treatment challenges to overcome. Studies with snake venom-derived proteins/peptides describe... (Review)
Review
Despite advances in treating patients with melanoma, there are still many treatment challenges to overcome. Studies with snake venom-derived proteins/peptides describe their binding potential, and inhibition of some proliferative mechanisms in melanoma. The combined use of these compounds with current therapies could be the strategic gap that will help us discover more effective treatments for melanoma. The present study aimed to carry out a systematic review identifying snake venom proteins and peptides described in the literature with antitumor, antimetastatic, or antiangiogenic effects on melanoma and determine the mechanisms of action that lead to these anti-tumor effects. Snake venoms contain proteins and peptides which are antiaggregant, antimetastatic, and antiangiogenic. The in vivo results are encouraging, considering the reduction of metastases and tumor size after treatment. In addition to these results, it was reported that these venom compounds could act in combination with chemotherapeutics (Acurhagin-C; Macrovipecetin), sensitizing and preparing tumor cells for treatment. There is a consensus that snake venom is a promising strategy for the improvement of antimelanoma therapies, but it has been little explored in the current context, combined with inhibitors, immunotherapy or tumor microenvironment, for example. We suggest Lebein as a candidate for combination therapy with BRAF inhibitors.
Topics: Humans; Snake Venoms; Melanoma; Peptides; Angiogenesis Inhibitors; Tumor Microenvironment
PubMed: 36690229
DOI: 10.1016/j.ijbiomac.2023.123367 -
PloS One 2022Atherosclerosis(AS) is widely recognized as a risk factor for incident cardiovascular and cerebrovascular diseases. Tetramethylpyrazine (TMP) is the active ingredient of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerosis(AS) is widely recognized as a risk factor for incident cardiovascular and cerebrovascular diseases. Tetramethylpyrazine (TMP) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against atherosclerosis.
OBJECTIVE
This systematic review and meta-analysis sought to study the impact of and mechanism of tetramethylpyrazine for atherosclerosis in animal models.
METHODS
A systematic search was conducted of PubMed, Embase, Cochrane Library, Web of Science database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI), WanFang data, and Vip Journal Integration Platform, covering the period from the respective start date of each database to December 2021. We used SYRCLE's 10-item checklist and Rev-Man 5.3 software to analyze the data and the risk of bias.
RESULTS
Twelve studies, including 258 animals, met the inclusion criteria. Compared with the control group, TMP significantly reduced aortic atherosclerotic lesion area, and induced significant decreases in levels of TC (SMD = -2.67, 95% CI -3.68 to -1.67, P < 0.00001), TG (SMD = -2.43, 95% CI -3.39 to -1.47, P < 0.00001), and LDL-C (SMD = -2.87, 95% CI -4.16 to -1.58, P < 0.00001), as well as increasing HDL-C (SMD = 2.04, 95% CI 1.05 to 3.03, P = 0.001). TMP also significantly modulated plasma inflammatory responses and biological signals associated with atherosclerosis. In subgroup analysis, the groups of high-dose TMP (≥50 mg/kg) showed better results than those of the control group. No difference between various durations of treatment groups or various assessing location groups.
CONCLUSION
TMP exerts anti-atherosclerosis functions in an animal model of AS mediated by anti-inflammatory action, antioxidant action, ameliorating lipid metabolism disorder, protection of endothelial function, antiplatelet activity, reducing the proliferation and migration of smooth muscle cells, inhibition of angiogenesis, antiplatelet aggregation. Due to the limitations of the quantity and quality of current studies, the above conclusions need to be verified by more high-quality studies.
TRIAL REGISTRATION NUMBER
PROSPERO registration no.CRD42021288874.
Topics: Animals; Aortic Diseases; Atherosclerosis; Disease Models, Animal; Humans; Pyrazines
PubMed: 35500001
DOI: 10.1371/journal.pone.0267968 -
Frontiers in Pharmacology 2022Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including...
Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including skilled personnel, medications, instruments, and funds. Thus, developing cancer prevention and treatment measures is necessary for healthcare personnel and patients alike. (Polygonaceae family) is a plant used as a culinary ingredient. It exhibits several pharmacological activities, such as antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer. Several classes of phytochemical constituents of have been reported. The important ones might be polyphenol and flavonoid derivatives. In this systematic review, the activities of against cancerous cells were determined and summarized. Data were obtained through a systematic search of electronic databases (EMBASE, PubMed, Scopus, Thai Thesis Database, Science Direct and Clinical Key). Eight studies met the eligibility criteria. The cancerous cell lines used in the studies were lymphoma, leukemia, oral, lung, breast, colon, and liver cancer cells. Based on this review, extracts significantly affected Epstein-Barr virus (EBV) genome-carrying human lymphoblastoid (Raji), mouse lymphocytic leukemia (P388), human acute lymphocytic leukemia (Jurkat), breast adenocarcinoma (MCF-7), human colon adenocarcinoma (HT-29), human T lymphoblast (MOLT-4), human promyelocytic leukemia cell line (HL-60), human hepatocellular carcinoma (HepG2), and oral squamous cell carcinoma (SAS, SCC-9, HSC-3) through induction of cell apoptosis, arrest of the cell cycle, inhibition of cell proliferation, migration, and colonization. The molecular mechanism of against cancers was reported to involve suppressing essential proteins required for cell proliferation, colonization, migration, apoptosis, and angiogenesis. They were survivin, cyclin-D, cyclooxygenase 2 (COX-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGF-A). The extract of was also involved in the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by inhibiting the expression of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR. From the key results of this review, is a promising chemotherapy and chemopreventive agent. Further investigation of its pharmacological activity and mechanism of action should be conducted using standardized extracts. experiments and clinical trials are required to confirm the anticancer activity.
PubMed: 35571080
DOI: 10.3389/fphar.2022.875016 -
Advanced Pharmaceutical Bulletin Sep 2021The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis... (Review)
Review
The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis stimulus in stem cells that is important for clinical application and engineering of functional cartilage. Hypoxia can potentially induce angiogenesis process by secretion of cytokines. This systematic review goal is to discover the effect of hypoxic condition on tendon/ ligament culture and the best oxygen level of hypoxia for in vitro and in vivo studies. We included 21 articles. A comprehensive review of this database confirms that the hypoxic condition is a substantial factor in the maintenance, proliferation, and differentiation of ligament/tendon cultures. Cell proliferation in the severe hypoxic (oxygen concentration of 1%) group at 24 h postcultivation was considered significant, but cell proliferation was markedly inhibited in the severe hypoxic group after 48 h.
PubMed: 34888206
DOI: 10.34172/apb.2021.069 -
The Cochrane Database of Systematic... Apr 2023Many women, and other females, with epithelial ovarian cancer (EOC) develop resistance to conventional chemotherapy drugs. Drugs that inhibit angiogenesis (development... (Review)
Review
BACKGROUND
Many women, and other females, with epithelial ovarian cancer (EOC) develop resistance to conventional chemotherapy drugs. Drugs that inhibit angiogenesis (development of new blood vessels), essential for tumour growth, control cancer growth by denying blood supply to tumour nodules.
OBJECTIVES
To compare the effectiveness and toxicities of angiogenesis inhibitors for treatment of epithelial ovarian cancer (EOC).
SEARCH METHODS
We identified randomised controlled trials (RCTs) by searching CENTRAL, MEDLINE and Embase (from 1990 to 30 September 2022). We searched clinical trials registers and contacted investigators of completed and ongoing trials for further information.
SELECTION CRITERIA
RCTs comparing angiogenesis inhibitors with standard chemotherapy, other types of anti-cancer treatment, other angiogenesis inhibitors with or without other treatments, or placebo/no treatment in a maintenance setting, in women with EOC. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our outcomes were overall survival (OS), progression-free survival (PFS), quality of life (QoL), adverse events (grade 3 and above) and hypertension (grade 2 and above).
MAIN RESULTS
We identified 50 studies (14,836 participants) for inclusion (including five studies from the previous version of this review): 13 solely in females with newly-diagnosed EOC and 37 in females with recurrent EOC (nine studies in platinum-sensitive EOC; 19 in platinum-resistant EOC; nine with studies with mixed or unclear platinum sensitivity). The main results are presented below. Newly-diagnosed EOC Bevacizumab, a monoclonal antibody that binds vascular endothelial growth factor (VEGF), given with chemotherapy and continued as maintenance, likely results in little to no difference in OS compared to chemotherapy alone (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.88 to 1.07; 2 studies, 2776 participants; moderate-certainty evidence). Evidence is very uncertain for PFS (HR 0.82, 95% CI 0.64 to 1.05; 2 studies, 2746 participants; very low-certainty evidence), although the combination results in a slight reduction in global QoL (mean difference (MD) -6.4, 95% CI -8.86 to -3.94; 1 study, 890 participants; high-certainty evidence). The combination likely increases any adverse event (grade ≥ 3) (risk ratio (RR) 1.16, 95% CI 1.07 to 1.26; 1 study, 1485 participants; moderate-certainty evidence) and may result in a large increase in hypertension (grade ≥ 2) (RR 4.27, 95% CI 3.25 to 5.60; 2 studies, 2707 participants; low-certainty evidence). Tyrosine kinase inhibitors (TKIs) to block VEGF receptors (VEGF-R), given with chemotherapy and continued as maintenance, likely result in little to no difference in OS (HR 0.99, 95% CI 0.84 to 1.17; 2 studies, 1451 participants; moderate-certainty evidence) and likely increase PFS slightly (HR 0.88, 95% CI 0.77 to 1.00; 2 studies, 2466 participants; moderate-certainty evidence). The combination likely reduces QoL slightly (MD -1.86, 95% CI -3.46 to -0.26; 1 study, 1340 participants; moderate-certainty evidence), but it increases any adverse event (grade ≥ 3) slightly (RR 1.31, 95% CI 1.11 to 1.55; 1 study, 188 participants; moderate-certainty evidence) and may result in a large increase in hypertension (grade ≥ 3) (RR 6.49, 95% CI 2.02 to 20.87; 1 study, 1352 participants; low-certainty evidence). Recurrent EOC (platinum-sensitive) Moderate-certainty evidence from three studies (with 1564 participants) indicates that bevacizumab with chemotherapy, and continued as maintenance, likely results in little to no difference in OS (HR 0.90, 95% CI 0.79 to 1.02), but likely improves PFS (HR 0.56, 95% CI 0.50 to 0.63) compared to chemotherapy alone. The combination may result in little to no difference in QoL (MD 0.8, 95% CI -2.11 to 3.71; 1 study, 486 participants; low-certainty evidence), but it increases the rate of any adverse event (grade ≥ 3) slightly (RR 1.11, 1.07 to 1.16; 3 studies, 1538 participants; high-certainty evidence). Hypertension (grade ≥ 3) was more common in arms with bevacizumab (RR 5.82, 95% CI 3.84 to 8.83; 3 studies, 1538 participants). TKIs with chemotherapy may result in little to no difference in OS (HR 0.86, 95% CI 0.67 to 1.11; 1 study, 282 participants; low-certainty evidence), likely increase PFS (HR 0.56, 95% CI 0.44 to 0.72; 1 study, 282 participants; moderate-certainty evidence), and may have little to no effect on QoL (MD 6.1, 95% CI -0.96 to 13.16; 1 study, 146 participants; low-certainty evidence). Hypertension (grade ≥ 3) was more common with TKIs (RR 3.32, 95% CI 1.21 to 9.10). Recurrent EOC (platinum-resistant) Bevacizumab with chemotherapy and continued as maintenance increases OS (HR 0.73, 95% CI 0.61 to 0.88; 5 studies, 778 participants; high-certainty evidence) and likely results in a large increase in PFS (HR 0.49, 95% CI 0.42 to 0.58; 5 studies, 778 participants; moderate-certainty evidence). The combination may result in a large increase in hypertension (grade ≥ 2) (RR 3.11, 95% CI 1.83 to 5.27; 2 studies, 436 participants; low-certainty evidence). The rate of bowel fistula/perforation (grade ≥ 2) may be slightly higher with bevacizumab (RR 6.89, 95% CI 0.86 to 55.09; 2 studies, 436 participants). Evidence from eight studies suggest TKIs with chemotherapy likely result in little to no difference in OS (HR 0.85, 95% CI 0.68 to 1.08; 940 participants; moderate-certainty evidence), with low-certainty evidence that it may increase PFS (HR 0.70, 95% CI 0.55 to 0.89; 940 participants), and may result in little to no meaningful difference in QoL (MD ranged from -0.19 at 6 weeks to -3.40 at 4 months). The combination increases any adverse event (grade ≥ 3) slightly (RR 1.23, 95% CI 1.02 to 1.49; 3 studies, 402 participants; high-certainty evidence). The effect on bowel fistula/perforation rates is uncertain (RR 2.74, 95% CI 0.77 to 9.75; 5 studies, 557 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Bevacizumab likely improves both OS and PFS in platinum-resistant relapsed EOC. In platinum-sensitive relapsed disease, bevacizumab and TKIs probably improve PFS, but may or may not improve OS. The results for TKIs in platinum-resistant relapsed EOC are similar. The effects on OS or PFS in newly-diagnosed EOC are less certain, with a decrease in QoL and increase in adverse events. Overall adverse events and QoL data were more variably reported than were PFS data. There appears to be a role for anti-angiogenesis treatment, but given the additional treatment burden and economic costs of maintenance treatments, benefits and risks of anti-angiogenesis treatments should be carefully considered.
Topics: Humans; Female; Angiogenesis Inhibitors; Bevacizumab; Carcinoma, Ovarian Epithelial; Vascular Endothelial Growth Factor A; Neoplasm Recurrence, Local; Ovarian Neoplasms
PubMed: 37185961
DOI: 10.1002/14651858.CD007930.pub3 -
Chinese Journal of Integrative Medicine Mar 2023Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of... (Review)
Review
Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis, exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore, drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and, consequently, consumed in diets. In this review, the systematic search strategy was used, which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy", in the electronic databases of PubMed, Cochrane Library, Web of Science and Scopus, from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties, including inhibition of cell proliferation, induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, impaired cell migration, invasion, tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO).
Topics: Humans; Flavonoids; Neoplasms; Antineoplastic Agents; Signal Transduction; Apoptosis; Cell Proliferation; Carcinogenesis; Cell Line, Tumor
PubMed: 35809179
DOI: 10.1007/s11655-022-3674-9 -
Critical Reviews in Oncology/hematology Mar 2021This review aimed to systematize and quantify the existing evidence about the effect of tumor vascularization on its growth, in preclinical studies. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This review aimed to systematize and quantify the existing evidence about the effect of tumor vascularization on its growth, in preclinical studies.
METHODOLOGY
A computerized research on databases PubMed, Scopus and EBSCO was performed to identify studies that evaluate both the vascularization parameters and the development of the tumors in animal models and the mean differences were calculated through a random effects model.
RESULTS
Thirteen studies met the inclusion criteria and were included in the systematic review, of which, 6 studies were included in the meta-analysis. Besides tumor vascular density that all studies evaluated, 3 studies analysed the tumor perfusion, 2 studies the tumor hypoxia and 3 studies assessed the grade of vessel maturation. Most of the studies (11) related decreased tumor vascularization and a concomitant inhibition of tumor growth or metastasis development. Quantitatively, the decrease in tumor vascularization contributed to a significant decrease in the tumor growing rate of 5.23 (-9.20, -1.26).
CONCLUSION
A reduced level of tumor vascularization seems to be able to inhibit tumor growth and progression.
Topics: Animals; Humans; Neoplasms; Neovascularization, Pathologic; Tumor Hypoxia
PubMed: 33508446
DOI: 10.1016/j.critrevonc.2021.103245 -
Neurosurgical Review Apr 2021Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit...
Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
Topics: Adrenergic beta-Antagonists; Brain Neoplasms; Cell Death; Cell Proliferation; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioblastoma; Glioma; Humans; Neovascularization, Pathologic
PubMed: 32172480
DOI: 10.1007/s10143-020-01277-4