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Synergistically Anti-Multiple Myeloma Effects: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib.Biomolecules Nov 2022Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has... (Review)
Review
Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has increased overall survival, progression-free survival, and remission rates in patients with MM since its clinical approval in 2003. However, the use of BTZ is challenged by the malignant features of MM and drug resistance. Polyphenols, classified into flavonoid and non-flavonoid polyphenols, have potential health-promoting activities, including anti-cancer. Previous preclinical studies have demonstrated the anti-MM potential of some dietary polyphenols. Therefore, these dietary polyphenols have the potential to be alternative therapies in anti-MM treatment regimens. This systematic review examines the synergistic effects of flavonoids and non-flavonoid polyphenols on the anti-MM impacts of BTZ. Preclinical studies on flavonoids and non-flavonoid polyphenols-BTZ synergism in MM were collected from PubMed, Web of Science, and Embase published between 2008 and 2020. 19 valid preclinical studies (Published from 2008 to 2020) were included in this systematic review. These studies demonstrated that eight flavonoids (icariin, icariside II, (-)-epigallocatechin-3-gallate, scutellarein, wogonin, morin, formononetin, daidzin), one plant extract rich in flavonoids (Punica granatum juice) and four non-flavonoid polyphenols (silibinin, resveratrol, curcumin, caffeic acid) synergistically enhanced the anti-MM effect of BTZ. These synergistic effects are mediated through the regulation of cellular signaling pathways associated with proliferation, apoptosis, and drug resistance. Given the above, flavonoids and non-flavonoid polyphenols can benefit MM patients by overcoming the challenges faced in BTZ treatment. Despite the positive nature of this preclinical evidence, some additional investigations are still needed before proceeding with clinical studies. For this purpose, we conclude by providing some suggestions for future research directions.
Topics: Humans; Bortezomib; Multiple Myeloma; Polyphenols; Apoptosis; Molecular Targeted Therapy; Cell Line, Tumor; Antineoplastic Agents; Drug Resistance, Neoplasm
PubMed: 36358997
DOI: 10.3390/biom12111647 -
Pharmaceutical Biology Dec 2022Accumulated experimental evidence suggests that resveratrol (RSV) may have an effect on acute kidney injury (AKI) by inhibiting inflammation. However, the credibility of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Accumulated experimental evidence suggests that resveratrol (RSV) may have an effect on acute kidney injury (AKI) by inhibiting inflammation. However, the credibility of the evidence for this practice is unclear.
OBJECTIVE
This study investigated the effect of RSV on AKI and the underlying mechanism.
METHODS
We searched PubMed, EMBASE, and Web of Science from 2005 to April 2022 for controlled animal trials assessing the effect of conventional resveratrol versus placebo on renal function outcome after AKI. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42022329596.
RESULTS
We retrieved 455 studies, 25 studies comprising data of 436 animals that met the inclusion criteria. Our meta-analysis suggested that RSV treatment was significantly associated with lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The greatest effects were recorded in low-dose (<20 mg/kg/day) groups rather than in high-dose (> 20 mg/kg/day) groups. For time-response effects, subgroup analysis indicated that intervention duration of RSV can influence the treatment effect, and more beneficial effects were observed when studies had a drug administration time of <2 weeks.
DISCUSSION AND CONCLUSIONS
This systematic review of animal AKI studies showed a consistently favourable effect of RSV as compared to placebo on renal function outcomes that increased with lower TNF-α, IL-6, and IL-1β. RSV has a more beneficial effect on SA-AKI animal models than the others. When the RSV intervention dose was low (< 20 mg/kg/day) and the intervention time was <2 weeks, more benefits could be observed.
Topics: Animals; Creatinine; Resveratrol; Tumor Necrosis Factor-alpha; Interleukin-6; Acute Kidney Injury; Anti-Inflammatory Agents; Kidney
PubMed: 36269038
DOI: 10.1080/13880209.2022.2132264 -
Nutrients Sep 2022Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control.
METHODS
MEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was -reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence.
RESULTS
We identified 64 controlled trials (91 trial comparisons, = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses.
CONCLUSIONS
Food source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control.
CLINICALTRIALS
gov: (NCT02716870).
Topics: Beverages; Biomarkers; C-Reactive Protein; Fructose; Interleukin-6; Sweetening Agents; Tumor Necrosis Factor-alpha
PubMed: 36235639
DOI: 10.3390/nu14193986 -
Phytomedicine : International Journal... Dec 2022Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of... (Review)
Review
BACKGROUND
Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products.
METHODS
A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria.
RESULTS
Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin.
CONCLUSION
Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9‑methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, β-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.
Topics: Acetates; Acrolein; Animals; Arbutin; Bleaching Agents; Cell Line, Tumor; Curcumin; Emodin; Flavonoids; Ginsenosides; Glucosides; Humans; Hydroxybenzoates; Melanins; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Phytochemicals; Plant Extracts; Pterocarpans; Stilbenes; Transcription Factors
PubMed: 36126406
DOI: 10.1016/j.phymed.2022.154449 -
Phytomedicine : International Journal... Dec 2022To explore the therapeutic effect and mechanism of Astragalus injection on viral myocarditis, we conducted a systematic review and meta-analysis to identify the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To explore the therapeutic effect and mechanism of Astragalus injection on viral myocarditis, we conducted a systematic review and meta-analysis to identify the influence of Astragalus injection on inflammatory mediators and overall efficiency in patients undergoing viral myocarditis.
METHODS
EMBASE, Cochrane Library, PubMed, Chinese Biomedical Literature, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched to screen randomized controlled trials (RCTs) published before July 3, 2022. The quality of participating studies was assessed by the Cochrane Collaboration Risk of Bias tool. The calculation of qualitative data used a risk ratio (RR) with a 95% confidence interval (95% CI), and quantitative data had standardized mean differences (SMDs) with a 95% CI. The heterogeneity among trials was quantified with Cochran's Q test and the I statistic. Confounding factors were estimated by sensitivity analysis, meta-regression, and subgroup analysis. The publication bias of participating articles was evaluated by funnel plot and Egger's test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was recommended for assessing the strength of evidence.
RESULTS
Nineteen available studies were included in our present meta-analysis, all of which were conducted in China. The outcomes expose that Astragalus injection dramatically decreased the levels of pro-inflammatory TNF-α (SMD=-2.271, 95% CI=-2.802 to -1.739, p<0.001, I=90.6%), IL-6 (SMD=-1.501, 95% CI=-1.872 to -1.130, p<0.001, I=83.2%), IL-17 (SMD=-3.194, 95% CI=-4.569 to -1.818, p<0.001, I=88.9%), 1L-8 (SMD=-6.133, 95% CI=-9.938 to -2.328, p = 0.002, I=97%), 1L-1 (SMD=-1.814, 95% CI=-2.557 to -1.070, p<0.001, I=92.1%), CRP (SMD=-2.020, 95% CI=-3.107 to -0.932, p<0.001, I=92.7%), and IFN-γ (SMD=-1.512, 95% CI=-2.771 to -0.253, p = 0.019, I=92%) and increased the total effective rate of treatment (RR=1.225, 95% CI=1.17 to 1.29, p<0.001, I=0.0%) in patients with viral myocarditis.
CONCLUSION
Astragalus injection can play a therapeutic role in patients with viral myocarditis through immunomodulatory effects. Outcomes were treated with caution due to significant heterogeneity among studies. Large-scale RCTs should be performed to support these conclusions.
Topics: Astragalus Plant; Humans; Inflammation Mediators; Interleukin-17; Interleukin-6; Myocarditis; Tumor Necrosis Factor-alpha
PubMed: 36115170
DOI: 10.1016/j.phymed.2022.154436 -
Toxicon : Official Journal of the... Oct 2022The genus Handroanthus Mattos (Bignoniaceae) is widely used for the treatment of cancer in traditional medicine in Brazil and other South American countries. The... (Review)
Review
The genus Handroanthus Mattos (Bignoniaceae) is widely used for the treatment of cancer in traditional medicine in Brazil and other South American countries. The anticancer potential of species of this genus has been reported in the literature, indicating that their chemical compounds may be effective against different tumor cell lines. In this perspective, the present study aimed to conduct a systematic review of ethnobotanical, pharmacological, phytochemical and toxicological information on Handroanthus species related to cancer treatment. Searches were conducted in the Google Scholar, PubMed®, ScienceDirect® and SciELO databases. A total of 78 articles published in the last thirty-two years (1990-2022) were eligible and included in the review. According to the scientific documents analyzed, five species of Handroanthus are widely used for the treatment of cancer in the traditional medicine of Brazil and other South American countries, including Bolivia and Argentina. The bark (88%) is the main part used in traditional preparations. Extracts and fractions from Handroanthus showed cytotoxicity against the following tumor cell lines: HL-60, MDA-MB-435, MDA-MB-231, MCF-7, HT-29, HCT-8, HCT-116, HEp-2, HepG2, CACO-2, SF-295, NCI-H292, NCI-H460, HeLa, and OVCAR-8. β-Lapachone, a naphthoquinone isolated from some species of this genus, is the most investigated compound for anticancer potential and has proved effective against some lung cancer cell lines (CL1-1, CL1-5 and A549). Results related to toxicological studies were not conclusive, considering that some extracts and compounds isolated from plants of this genus may present some degree of toxicity depending on the time of use and the concentration/dose used. Thus, despite the promising effects against various cancer cell lines, caution is needed when making use of these products.
Topics: Bignoniaceae; Brazil; Caco-2 Cells; Ethnopharmacology; Humans; Phytotherapy; Plant Extracts; Plants, Medicinal
PubMed: 35998713
DOI: 10.1016/j.toxicon.2022.08.007 -
Phytomedicine : International Journal... Oct 2022Many substances derived from nutritional or medicinal plants have been studied for their chemopreventive and antineoplastic properties. Among those studied, Ficus carica... (Review)
Review
BACKGROUND
Many substances derived from nutritional or medicinal plants have been studied for their chemopreventive and antineoplastic properties. Among those studied, Ficus carica has shown to have a significant ability to inhibit tumor formation and development of cancer cells through modulating various signaling mechanisms and interaction including a large number of cell signaling molecules.
PURPOSE
The goal of this study is to provide a critical and complete evaluation of F. carica's anticancer capacity in various malignancies, as well as related molecular targets.
METHODS
Research was conducted electronically on scholarly scientific databases, including Science Direct, PubMed, and Scopus. Published papers were analyzed and investigated using the keywords, Ficus carica, figs, cancer, malignancies and tumor based on established selection criteria. In this systematic review, 27 individual studies were considered.
RESULTS
Treatment with F. carica alone or in combination with other medications was linked to anticancer activity with significant evidence. Furthermore, F. carica has been shown to use multitargeted pathways to prevent cancer initiation and development by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, apoptosis, autophagy inflammatory processes, metastasis, invasion, and angiogenesis.
CONCLUSION
Our findings suggest that F. carica and its phytochemicals have the potential for cancer prevention and therapy. Nonetheless, additional mechanistic studies with pure compounds derived from F. carica and well-designed clinical trials are needed to advance our knowledge to clinical application.
Topics: Carica; Ficus; Humans; Neoplasms; Phytochemicals; Plant Extracts; Plants, Medicinal
PubMed: 35952577
DOI: 10.1016/j.phymed.2022.154333 -
Complementary Medicine Research 2022Cancer is a common disease in humans and in companion animals and treatment is challenging. The aim of this systematic review was to identify and assess the potential...
Cancer is a common disease in humans and in companion animals and treatment is challenging. The aim of this systematic review was to identify and assess the potential use of Viscum album L. extracts (VAE) for treatment of neoplastic diseases in companion animals. Peer-reviewed animal, in vivo and in vitro studies were included, considering the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and A Measurement Tool to Assess Systematic Reviews (AMSTAR). Overall, 6,148 references were identified. Following a predefined protocol, 114 full-text references were assessed. Ultimately, 61 references were included for further assessment, 25 references included in vitro experiments, 26 included in vivo and clinical experiments, and 10 references included both in vitro and in vivo experiments. These 61 references comprised data of 193 in vitro and 67 in vivo and clinical experiments. Most of the 67 in vivo and clinical experiments were conducted with mice (59), followed by rats (4), dogs (3), and horses (1). So far, oral melanomas, mammary tumors, and sticker sarcomas in dogs, as well as sarcoids in horses, have been investigated in controlled clinical trials. A scoring system was established to evaluate the outcomes of each study based on defined effect levels. The efficacy of VAE treatment was most pronounced for melanomas, sarcomas, mammary carcinoma, and equine sarcoids. The limited number and quality of published studies on VAE treatment in companion animals impede drawing definitive conclusions regarding the efficacy of VAE in the treatment of cancer. Thus, further research is needed to elucidate the impact of VAE on the treatment of cancer in companion animals and possible underlying mechanisms.
Topics: Horses; Animals; Dogs; Humans; Mice; Rats; Female; Viscum album; Melanoma; Plant Extracts; Mouth Neoplasms; Breast Neoplasms
PubMed: 35810741
DOI: 10.1159/000525035 -
Phytotherapy Research : PTR Sep 2022The beneficial effects of Ginkgo biloba on cardio-metabolic markers have been reported. However, its effect on inflammation is not assessed in any meta-analysis. We... (Meta-Analysis)
Meta-Analysis Review
The beneficial effects of Ginkgo biloba on cardio-metabolic markers have been reported. However, its effect on inflammation is not assessed in any meta-analysis. We performed a systematic review of randomized controlled trials evaluating the effects of Ginkgo biloba leaf extract (GBLE) on serum C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. A systematic search was performed on four databases, including PubMed, Scopus, Web of Science, and Google Scholar, up to October 2021. After screening, 17 trials met our inclusion criteria. Trials were of 1-24 weeks of duration and included 1,104 participants. In the meta-analysis, the weighted mean differences (WMD) in change for serum CRP were -1.5 mg/L (95% CI: -2.16, -0.85, p < 0.001). Moreover, WMD for serum IL-6 and TNF-α were in favor of the GBLE compared to the placebo [(-16.86 pg/mL, 95% CI: -19.38, -14.34, p < 0.001); and (-4.19 pg/mL, 95%CI: -5.14, -3.23, p < 0.001), respectively]. Subgroup analysis showed that GBLE has a beneficial effect on serum CRP at the baseline levels≥3 mg/L and doses<500 mg/day. This meta-analysis showed that the GBLE could reduce serum inflammatory markers. Therefore, this medicinal herb might be a possible strategy for inflammation control.
Topics: Biomarkers; C-Reactive Protein; Dietary Supplements; Ginkgo biloba; Humans; Inflammation; Interleukin-6; Plant Extracts; Tumor Necrosis Factor-alpha
PubMed: 35781715
DOI: 10.1002/ptr.7544 -
Journal of Ethnopharmacology Nov 2022Ilex rotunda Thunb. (I. rotunda) is an Ilex species of Aquifoliaceae, widely distributed in East Asia. Its dried bark is commonly used as a medicinal part in the field... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Ilex rotunda Thunb. (I. rotunda) is an Ilex species of Aquifoliaceae, widely distributed in East Asia. Its dried bark is commonly used as a medicinal part in the field of traditional Chinese medicine (TCM), named Ilicis Rotundae Cortex. This medicinal plant is commonly used for clearing heat and removing toxin, draining dampness and relieving pain in TCM to treat tonsillitis, acute gastroenteritis, gastric and duodenal ulcer, rheumatism, traumatic injury, and so on. It also has significant development value on lipid-lowering, hepatoprotection and anti-inflammation, but the potential mechanism needs to be further explored.
AIM OF THE REVIEW
More and more medicinal substances are being discovered in I. rotunda with multiple biological activities, which help to advance the ethno-pharmacological research in I. rotunda. However, to date there is a lack of a systematic summary of research progress on I. rotunda. This review aims to provide a critical summary of the current studies on I. rotunda. The progress in research on botany, phytochemistry, traditional uses, pharmacology, toxicology, quality control and pharmacokinetics of the plant is discussed. It hopes to provide useful references and guidance for the future directions of research on I. rotunda.
MATERIALS AND METHODS
Studies of I. rotunda were collected via Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. The literature cited in this review covered the period from 1956 to January 2022.
RESULTS
Analysis of the literature indicates that I. rotunda is a potentially valuable herbal medicine for the therapeutic of various diseases. To date, 120 compounds were found and identified in I. rotunda, mainly including triterpenoids, phenylpropanoids, etc. Modern pharmacological studies also found that the plant has the activities of protecting the cardiovascular system, lowering lipids and protecting the liver, as well as being an anti-inflammatory, anti-tumor and antibacterial.
CONCLUSIONS
This review summarizes the results from current studies of I. rotunda. However, the current explanation seems insufficient and unsatisfactory, in terms of the relationships between the traditional uses and the modern pharmacological activities, the mechanisms and the material basis. Thus, a critical and comprehensive evaluation is necessary to explore its future research prospects and development direction.
Topics: Botany; Drugs, Chinese Herbal; Ethnopharmacology; Ilex; Medicine, Chinese Traditional; Phytochemicals; Phytotherapy; Plants, Medicinal; Quality Control
PubMed: 35781006
DOI: 10.1016/j.jep.2022.115419