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Wang T, Sun J, Wang L, Lin Y, Wu Z, Jia Q, Zhang S, An J, Ma X, Wu Q, Su Z, Wang H. Therapeutic potential of isochlorogenic acid A from Taraxacum officinale in improving immune response and enhancing the efficacy of PD-1/PD-L1 blockade in triple-negative breast cancer. Front Immunol 2025; 16:1529710. [PMID: 40109332 PMCID: PMC11920172 DOI: 10.3389/fimmu.2025.1529710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Accepted: 02/19/2025] [Indexed: 03/22/2025] Open
Abstract
Introduction Taraxacum officinale, a traditional medicinal herb, has garnered significant attention for its potential role in the prevention and treatment of breast cancer. Although clinical recognition of its efficacy has gradually increased, research has shown that Taraxacum officinale contains a variety of chemical components, including triterpenes, carbohydrates, flavonoids, phenolic acids, sesquiterpenes, coumarins, fatty acids, and organic acids. However, the pharmacological mechanisms underlying Taraxacum officinale's effects and the identification of its key bioactive components warrant further investigation. Methods Flow cytometry was utilized to investigate the effects of Taraxacum officinale extract (TOE) in combination with PD-1/PD-L1 inhibitor 2 on the immune microenvironment of triple-negative breast cancer (TNBC). Active compounds and their potential targets were identified through an integrative approach involving GeneCards, OMIM, and DisGeNET databases, as well as UPLC-Q-Orbitrap MS analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, followed by molecular docking to explore compound-target interactions. The anti-proliferative effects of isochlorogenic acid A (ICGA-A) and chicoric acid (CRA) on MDA-MB-231 and 4T1 cells were evaluated using the CCK-8 assay. In vivo validation was performed using a 4T1 murine model and flow cytometry. Results TOE and its active constituents, ICGA-A and CRA, demonstrate potential in augmenting PD-1 blockade therapy for TNBC. This study investigated the combination of ICGA-A and PD-1/PD-L1 inhibitor 2, which significantly enhanced the infiltration of macrophages and CD8+ T cells into tumors in murine models, while concurrently reducing the population of exhausted T cells. Furthermore, CRA notably increased the frequency of CD8+ T cells. Both ICGA-A and CRA therapies were also found to suppress tumor proliferation by inhibiting the FAK/PI3K/AKT/mTOR signaling pathway. These findings highlight the potential of ICGA-A and CRA as effective adjuvants to improve the therapeutic efficacy of PD-1 inhibitor-based immunotherapy in TNBC. Discussion ICGA-A and CRA, bioactive compounds from Taraxacum officinale, exhibit significant antitumor activity in TNBC by targeting the FAK/PI3K/AKT/mTOR pathway, a critical regulator of cancer progression. Their ability to modulate the tumor immune microenvironment highlights their potential as immune modulators that enhance the efficacy of immunotherapy. These findings suggest that ICGA-A and CRA could serve as promising adjuncts in TNBC treatment, offering a novel strategy to overcome challenges such as therapeutic resistance and limited treatment options. Further investigation is warranted to explore their synergistic effects with immunotherapies in improving TNBC outcomes.
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Affiliation(s)
- Tangyi Wang
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
| | - Jingwei Sun
- Department of Medical Laboratory, Qinghai Provincial People’s Hospital, Xining, Qinghai, China
| | - Li Wang
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
| | - Yuxin Lin
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
| | - Zhijing Wu
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
| | - Qiangqiang Jia
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai, China
| | - Shoude Zhang
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai, China
| | - Juan An
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
- Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, China
- Key Laboratory of the Ministry of High Altitude Medicine, Qinghai University, Xining, Qinghai, China
| | - Xueman Ma
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
- Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, China
- Key Laboratory of the Ministry of High Altitude Medicine, Qinghai University, Xining, Qinghai, China
| | - Qiong Wu
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
- Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, China
- Key Laboratory of the Ministry of High Altitude Medicine, Qinghai University, Xining, Qinghai, China
| | - Zhanhai Su
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
- Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, China
- Key Laboratory of the Ministry of High Altitude Medicine, Qinghai University, Xining, Qinghai, China
| | - Haiyan Wang
- Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, China
- Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, China
- Key Laboratory of the Ministry of High Altitude Medicine, Qinghai University, Xining, Qinghai, China
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Wu J, Sun J, Liu M, Zhang X, Kong L, Ma L, Jiang S, Liu X, Ma W. Botany, Traditional Use, Phytochemistry, Pharmacology and Quality Control of Taraxaci herba: Comprehensive Review. Pharmaceuticals (Basel) 2024; 17:1113. [PMID: 39338278 PMCID: PMC11434673 DOI: 10.3390/ph17091113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/20/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024] Open
Abstract
Taraxaci herba, as a traditional Chinese medicine, is the name of the Taraxacum genus in the Asteraceae family. Documented in the Tang Herbal Medicine (Tang Dynasty, AD 657-659), its medicinal properties cover a wide range of applications such as acute mastitis, lung abscess, conjunctival congestion, sore throat, damp-heat jaundice, and vision improvement. In the Chinese Pharmacopoeia (Edition 2020), more than 40 kinds of China-patented drugs containing Taraxaci herba were recorded. This review explores the evolving scientific understanding of Taraxaci herba, covering facets of ethnopharmacology, botany, phytochemistry, pharmacology, artificial cultivation, and quality control. In particular, the chemical constituents and pharmacological research are reviewed. Taraxaci herba has been certified as a traditional medicine plant, and its flavonoids, phenolic acids, and terpenoids have been identified and separated, which include Chicoric acid, taraxasterol, Taraxasteryl acetate, Chlorogenic acid, isorhamnetin, and luteolin; they are responsible for anti-inflammatory, antioxidant, antibacterial, anti-tumor, and anti-cancer activities. These findings validate the traditional uses of Taraxaci herba and lay the groundwork for further scientific exploration. The sources used in this study include Web of Science, Pubmed, the CNKI site, classic monographs, the Chinese Pharmacopoeia, the Chinese Medicine Dictionary, and doctoral and master's theses.
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Affiliation(s)
- Jianhao Wu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Jialin Sun
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Meiqi Liu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Xiaozhuang Zhang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Lingyang Kong
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Lengleng Ma
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Shan Jiang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
| | - Xiubo Liu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
- School of Jiamusi, Heilongjiang University of Chinese Medicine, Jiamusi 154007, China
| | - Wei Ma
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150006, China
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Srivastava G, Mukherjee E, Mittal R, Ganjewala D. Geraniol and citral: recent developments in their anticancer credentials opening new vistas in complementary cancer therapy. Z NATURFORSCH C 2024; 79:163-177. [PMID: 38635829 DOI: 10.1515/znc-2023-0150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 04/03/2024] [Indexed: 04/20/2024]
Abstract
About 10 million people are diagnosed with cancer each year. Globally, it is the second leading cause of death after heart disease, and by 2035, the death toll could reach 14.6 million. Several drugs and treatments are available to treat cancer, but survival rates remain low. Many studies in recent years have shown that plant-derived monoterpenes, particularly geraniol and citral, are effective against various cancers, including breast, liver, melanoma, endometrial, colon, prostate, and skin cancers. This trend has opened new possibilities for the development of new therapeutics or adjuvants in the field of cancer therapy. These monoterpenes can improve the efficacy of chemotherapy by modulating many signaling molecules and pathways within tumors. Analysis of reports on the anticancer effects published in the past 5 years provided an overview of the most important results of these and related properties. Also, the molecular mechanisms by which they exert their anticancer effects in cell and animal studies have been explained. Therefore, this review aims to highlight the scope of geraniol and citral as complementary or alternative treatment options in cancer therapy.
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Affiliation(s)
- Gauri Srivastava
- Amity Institute of Biotechnology, 77282 Amity University , Sector-125, Noida 201303, Uttar Pradesh, India
| | - Esha Mukherjee
- Amity Institute of Biotechnology, 77282 Amity University , Sector-125, Noida 201303, Uttar Pradesh, India
| | - Ruchika Mittal
- Amity Institute of Biotechnology, 77282 Amity University , Sector-125, Noida 201303, Uttar Pradesh, India
| | - Deepak Ganjewala
- Amity Institute of Biotechnology, 77282 Amity University , Sector-125, Noida 201303, Uttar Pradesh, India
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Hao F, Deng X, Yu X, Wang W, Yan W, Zhao X, Wang X, Bai C, Wang Z, Han L. Taraxacum: A Review of Ethnopharmacology, Phytochemistry and Pharmacological Activity. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2024; 52:183-215. [PMID: 38351703 DOI: 10.1142/s0192415x24500083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
Taraxacum refers to the genus Taraxacum, which has a long history of use as a medicinal plant and is widely distributed around the world. There are over 2500 species in the genus Taraxacum recorded as medicinal plants in China, Central Asia, Europe, and the Americas. It has traditionally been used for detoxification, diuresis, liver protection, the treatment of various inflammations, antimicrobial properties, and so on. We used the most typically reported Taraxacum officinale as an example and assembled its chemical makeup, including sesquiterpene, triterpene, steroids, flavone, sugar and its derivatives, phenolic acids, fatty acids, and other compounds, which are also the material basis for its pharmacological effects. Pharmacological investigations have revealed that Taraxacum crude extracts and chemical compounds contain antimicrobial infection, anti-inflammatory, antitumor, anti-oxidative, liver protective, and blood sugar and blood lipid management properties. These findings adequately confirm the previously described traditional uses and aid in explaining its therapeutic applications.
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Affiliation(s)
- Fusheng Hao
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Xinxin Deng
- Department of Integration of Chinese and Western Medicine, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing 100142, P. R. China
| | - Xin Yu
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Wen Wang
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Wei Yan
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Xi Zhao
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Xiaofei Wang
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Changcai Bai
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Zhizhong Wang
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, P. R. China
| | - Lu Han
- School of Pharmacy, Ningxia Medical University, Yinchuan 750004, P. R. China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, P. R. China
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Rezaie H, Alipanah-Moghadam R, Jeddi F, Clark CCT, Aghamohammadi V, Nemati A. Combined dandelion extract and all-trans retinoic acid induces cytotoxicity in human breast cancer cells. Sci Rep 2023; 13:15074. [PMID: 37700002 PMCID: PMC10497591 DOI: 10.1038/s41598-023-42177-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 09/06/2023] [Indexed: 09/14/2023] Open
Abstract
Breast cancer is one of the most prevalent and deadly cancers among women worldwide. Recently, natural compounds have been widely used for the treatment of breast cancer. Present study evaluated antiproliferative and anti-metastasis activities of two natural compounds of dandelion and all-trans-retinoic acid (ATRA) in human MCF-7 and MDA-MB231 breast cancer cells. We also evaluated the expression of MMP-2, MMP-9, IL-1β, p53, NM23 and KAI1 genes. Data showed a clear additive cytotoxic effect in concentrations of 40 μM ATRA with 1.5 and 4 mg/ml of dandelion extract in MCF-7 and MDA-MB231 cells, respectively. In both cell lines, compared with the untreated cells, the expression levels of MMP-9 and IL-1β were significantly decreased while p53 and KAI1 expression levels were increased. Besides, MMP-2 and NM23 had different expressions in the two studied cell lines. In conclusion, dandelion/ATRA co-treatment, in addition to having strong cytotoxic effects, has putative effects on the expression of anti-metastatic genes in both breast cancer cells.
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Affiliation(s)
- Hamed Rezaie
- Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Reza Alipanah-Moghadam
- Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
| | - Farhad Jeddi
- Department of Genetics and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, CV1 5FB, UK
| | | | - Ali Nemati
- Department of Clinical Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
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Türkmen BM, Teyin G, Lokman U, Memis Kocaman E. Functional Effects of Dandelion ( Taraxacum officinale) and Its Use in the Traditional Cuisines. JOURNAL OF CULINARY SCIENCE & TECHNOLOGY 2023. [DOI: 10.1080/15428052.2022.2163733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Büşra Meltem Türkmen
- Department of Gastronomy and Culinary Arts, Istanbul Medipol University, Istanbul, Turkey
| | - Görkem Teyin
- Department of Gastronomy and Culinary Arts, Doğuş University, Istanbul, Turkey
| | - Uğur Lokman
- Gastronomy and Culinary Arts, Nevsehir Haci Bektas Veli Universitesi, Istanbul, Turkey
| | - Emel Memis Kocaman
- Department of Gastronomy and Culinary Arts, Tokat Gaziosmanpasa University, Tokat, Turkey
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Muruthi CW, Ngugi MP, Runo SM, Mwitari PG. In Vitro Antiproliferative Effects and Phytochemical Characterization of Carissa edulis ((Forssk) Vahl) and Pappea capensis (Eckyl and Zeyh) Extracts. J Evid Based Integr Med 2023; 28:2515690X231187711. [PMID: 37489007 PMCID: PMC10387709 DOI: 10.1177/2515690x231187711] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 05/30/2023] [Accepted: 06/24/2023] [Indexed: 07/26/2023] Open
Abstract
Cancer mortality is a global concern. The current therapeutic approaches despite showing efficacy are characterized by several limitations. Search for alternatives has led to the use of herbal plants including C. edulis and P. capensis. However, there is limited research on antiproliferative effects of these medicinal plants. The study sought to evaluate antiproliferative effects of the plants against human breast and prostate cancers using cell viability, and gene expression assays to determine modulation of apoptotic genes. Further, Liquid Chromatography Mass Spectrophotometer (LC-MS) and Gas Chromatography Mass Spectrophotometer (GC-MS) analyses were performed to confirm phytocompounds in the extracts. The results indicated that ethylacetate extracts of C. edulis and P. capensis had the highest activity against cancer cells with IC50 values of 2.12 ± 0.02, and 6.57 ± 0.03 μg/ml on HCC 1395 and 2.92 ± 0.17 and 5.00 ± 0.17 μg/ml on DU145, respectively. Moreover, the plants extracts exhibited relatively less cytotoxic activities against Vero cell lines (IC50 > 20 μg/ml). The extracts also exhibit selectivity against the cancer cells (SI > 3). Further, mRNA expression of p53 in the treated HCC 1395 was increased by 7 and 3-fold, whereas by 3 and 2-fold in DU145 cells, upon treatment with ethylacetate extracts of C. edulis and P. capensis, respectively. Similarly, several-fold increases were observed in the number of transcripts of Bax in HCC 1395 and HOXB13 in DU145 cells. Phytochemical analyses detected presence of phytocompounds including flavonoids, phenolics, tocopherols and terpenoids which are associated with anticancer activity. Findings from this study provide a scientific validation for the folklore use of these plants in management of cancer.
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Affiliation(s)
- Carolyn Wanjira Muruthi
- Department of Biochemistry, Microbiology and Biotechnology-Kenyatta University, Nairobi, Kenya
| | - Mathew Piero Ngugi
- Department of Biochemistry, Microbiology and Biotechnology-Kenyatta University, Nairobi, Kenya
| | - Steven Maina Runo
- Department of Biochemistry, Microbiology and Biotechnology-Kenyatta University, Nairobi, Kenya
| | - Peter Githaiga Mwitari
- Centre for Traditional Medicine and Drug Research-Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
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Liu FJ, Yang J, Chen XY, Yu T, Ni H, Feng L, Li P, Li HJ. Chemometrics integrated with in silico pharmacology to reveal antioxidative and anti-inflammatory markers of dandelion for its quality control. Chin Med 2022; 17:125. [PMCID: PMC9636813 DOI: 10.1186/s13020-022-00679-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022] Open
Abstract
Abstract
Background
Dandelion is an herb with high nutritional and medicinal values, which has been listed in Chinese Pharmacopeia, European Pharmacopoeia and British Pharmacopoeia, gaining increasing acceptance around the world. However, the current quality control of dandelion is lagging behind. Only in Chinese Pharmacopeia, cichoric acid is used as a marker compound for its quality evaluation, whereas, it can not comprehensively reflect the bioactivity of dandelion.
Methods
This study developed a strategy by integrating chemometrics with in silico pharmacology to reveal the bioactive markers of dandelion for its quality control. Firstly, the major chemicals in dandelion were characterized using HPLC-DAD-MS/MS, and the corresponding antioxidant and anti-inflammatory activities were evaluated in vitro. Subsequently, the active components were screened by relating the chemicals and bioactivity of dandelion via grey relational assay and partial least squares regression analysis. The potential active components were then subjected to a validation for their activities. Moreover, in silico pharmacology was utilized to evaluate the contribution of active components to efficacy.
Results
A total of 22 phenolic compounds were characterized. Among them, cichoric acid, caffeic acid and luteolin were identified as quality markers owing to their good correlations with the bioactivities of dandelion. These three markers were quantified in frequently-used dandelion species, viz. Taraxacum mongolicum Hand.-Mazz. (TAM) and T. officinale F. H. Wigg. (TAO). TAM, with acceptably higher content of cichoric acid and caffeic acid, showed better antioxidant activity than TAO. While TAO included higher content of luteolin, presenting slightly more effective in anti-inflammation.
Conclusion
An useful strategy for the quality marker discovery was successfully designed. And the results provided more knowledge for the quality evaluation of dandelion.
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Dhyani P, Sati P, Sharma E, Attri DC, Bahukhandi A, Tynybekov B, Szopa A, Sharifi-Rad J, Calina D, Suleria HAR, Cho WC. Sesquiterpenoid lactones as potential anti-cancer agents: an update on molecular mechanisms and recent studies. Cancer Cell Int 2022; 22:305. [PMID: 36207736 PMCID: PMC9540722 DOI: 10.1186/s12935-022-02721-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/22/2022] [Indexed: 11/28/2022] Open
Abstract
Plants-based natural compounds are well-identified and recognized chemoprotective agents that can be used for primary and secondary cancer prevention, as they have proven efficacy and fewer side effects. In today's scenario, when cancer cases rapidly increase in developed and developing countries, the anti-cancerous plant-based compounds become highly imperative. Among others, the Asteraceae (Compositae) family's plants are rich in sesquiterpenoid lactones, a subclass of terpenoids with wide structural diversity, and offer unique anti-cancerous effects. These plants are utilized in folk medicine against numerous diseases worldwide. However, these plants are now a part of the modern medical system, with their sesquiterpenoid lactones researched extensively to find more effective and efficient cancer drug regimens. Given the evolving importance of sesquiterpenoid lactones for cancer research, this review comprehensively covers different domains in a spectrum of sesquiterpenoid lactones viz (i) Guaianolides (ii) Pseudoguaianolide (iii) Eudesmanolide (iv) Melampodinin A and (v) Germacrene, from important plants such as Cynara scolymus (globe artichoke), Arnica montana (wolf weeds), Spilanthes acmella, Taraxacum officinale, Melampodium, Solidago spp. The review, therefore, envisages being a helpful resource for the growth of plant-based anti-cancerous drug development.
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Affiliation(s)
- Praveen Dhyani
- Department of Biotechnology, Kumaun University, Bhimtal, 263 136 Uttarakhand India
| | - Priyanka Sati
- Graphic Era University, Dehradun, 248 001 Uttarakhand India
| | - Eshita Sharma
- Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, 143 005 Punjab India
| | - Dharam Chand Attri
- High Altitude Plant Physiology Research Centre (HAPPRC), HNB Garhwal University, Srinagar Garhwal, 246 174 Uttarakhand India
| | - Amit Bahukhandi
- G.B. Pant National Institute of Himalayan Environment, Kosi-Katarmal, Almora, 263 643 Uttarakhand India
| | - Bekzat Tynybekov
- Department of Biodiversity of Bioresources, Al-Farabi Kazakh National University, Almaty, Kazakhstan
| | - Agnieszka Szopa
- Department of Pharmaceutical Botany, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
| | | | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Hafiz A. R. Suleria
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010 Australia
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong China
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Phytochemical Analysis and In Vitro Cytotoxic Activity against Colorectal Adenocarcinoma Cells of Hippophae rhamnodies L., Cymbopogon citratus (D.C.) Stapf, and Ocimum basilicum L. Essential Oils. PLANTS 2021; 10:plants10122752. [PMID: 34961223 PMCID: PMC8704097 DOI: 10.3390/plants10122752] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 11/17/2022]
Abstract
Colorectal carcinoma (CRC) is one of the most frequently diagnosed cancer types with current deficient and aggressive treatment options, but various studied alternative therapies are able to efficiently contribute to its management. Essential oils (EOs) contain valuable compounds, with antibacterial, anti-inflammatory, and anticancer properties, which might serve as effective solutions in CRC prophylaxis or treatment. The aim of the present work was to evaluate the phytochemical composition and in vitro biological activity of essential oils derived from Hippophae rhamnoides (Hr_EO), Cymbopogon citratus (Cc_EO), and Ocimum basilicum (Ob_EO) species on HT-29 and Caco-2 human colorectal adenocarcinoma cell lines. The main compounds identified by GC-MS analysis were estragole (Hr_EO, Ob_EO), alpha- and beta-citral (Cc_EO). All tested EOs exerted a dose-dependent cytotoxicity on both cell lines by reducing the cell viability, especially in the case of Cc_EO, where at 75 µg/mL the viability percentages reached the values of 62.69% (Caco-2) and 64.09% (HT-29), respectively. The nuclear morphology evaluation highlighted significant dysmorphologies on both lines after their treatment with EOs at 75 µg/mL.
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Man J, Wu L, Han P, Hao Y, Li J, Gao Z, Wang J, Yang W, Tian Y. Revealing the metabolic mechanism of dandelion extract against A549 cells using UPLC-QTOF MS. Biomed Chromatogr 2021; 36:e5272. [PMID: 34727378 DOI: 10.1002/bmc.5272] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 10/19/2021] [Accepted: 10/23/2021] [Indexed: 11/08/2022]
Abstract
Dandelion extract shows potential anticancer activity and is expected to be a new type of natural anti-cancer drug. However, the effect mechanism of dandelion extract to lung cancer cells is still unclear. Here, untargeted metabolomics approach based on liquid chromatography-mass spectrograph (LC-MS) was used to characterize the metabolic responses of A549 cell to dandelion extract exposure, to provide new clues for the anti-tumor mechanism of dandelion extract from the perspective of metabolomics. A total of 16 differentially expressed and time-related metabolites were identified between dandelion extract exposure and control groups. The perturbed metabolic pathways of A549 cells after dandelion extract exposure mainly include the glycerophospholipid metabolism and purine metabolism. These results concluded that dandelion extract may exert anticancer activity by affecting the malignant proliferation, disturbing the stability of cell membrane structure, reducing the adhesion of tumor cells to extracellular matrix and fibronectin and finally inducing tumor cell death.
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Affiliation(s)
- Jin Man
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | | | - Pei Han
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Yun Hao
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Jiaying Li
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Zibo Gao
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Jia Wang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Wenjie Yang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Yongmei Tian
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China
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12
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Bai B, Chen Q, Jing R, He X, Wang H, Ban Y, Ye Q, Xu W, Zheng C. Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents. Front Pharmacol 2021; 12:738235. [PMID: 34630112 PMCID: PMC8495205 DOI: 10.3389/fphar.2021.738235] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022] Open
Abstract
Prostate cancer is the second most common malignant cancer in males. It involves a complex process driven by diverse molecular pathways that closely related to the survival, apoptosis, metabolic and metastatic characteristics of aggressive cancer. Prostate cancer can be categorized into androgen dependent prostate cancer and castration-resistant prostate cancer and cure remains elusive due to the developed resistance of the disease. Natural compounds represent an extraordinary resource of structural scaffolds with high diversity that can offer promising chemical agents for making prostate cancer less devastating and curable. Herein, those natural compounds of different origins and structures with potential cytotoxicity and/or in vivo anti-tumor activities against prostate cancer are critically reviewed and summarized according to the cellular signaling pathways they interfere. Moreover, the anti-prostate cancer efficacy of many nutrients, medicinal plant extracts and Chinese medical formulations were presented, and the future prospects for the application of these compounds and extracts were discussed. Although the failure of conventional chemotherapy as well as involved serious side effects makes natural products ideal candidates for the treatment of prostate cancer, more investigations of preclinical and even clinical studies are necessary to make use of these medical substances reasonably. Therefore, the elucidation of structure-activity relationship and precise mechanism of action, identification of novel potential molecular targets, and optimization of drug combination are essential in natural medicine research and development.
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Affiliation(s)
- Bingke Bai
- Department of Chinese Medicine Authentication, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Qianbo Chen
- Department of Anesthesiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Rui Jing
- Department of Chinese Medicine Authentication, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Xuhui He
- Department of Chinese Medicine Authentication, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Hongrui Wang
- Department of Chinese Medicine Authentication, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Yanfei Ban
- Department of Chinese Medicine Authentication, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Qi Ye
- Department of Biological Science, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Weiheng Xu
- Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Chengjian Zheng
- Department of Chinese Medicine Authentication, School of Pharmacy, Second Military Medical University, Shanghai, China
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Mwamatope B, Tembo D, Chikowe I, Maliwichi-Nyirenda C, Kampira E, Masumbu FF. Ethnobotanical Study of Medicinal Plants Used for Management of Cancer in Karonga District, Northern Malawi. Anticancer Agents Med Chem 2021; 22:1622-1631. [PMID: 34238201 DOI: 10.2174/1871520621666210708122037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 04/10/2021] [Accepted: 04/18/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND In Malawi, cancer is one of the leading causes of morbidity and mortality. This has led to increased use of herbal medicines for cancer management. OBJECTIVE This study aimed at identifying medicinal plants that are used for the management of cancer in the southern area of Karonga district, Northern Malawi. METHODS Semi-structured individual questionnaire interviews were used to collect ethnobotanical data from traditional herbal practitioners in the study area. RESULTS A total of twenty-six (26) plant species from seventeen (17) botanical families were reported by Traditional Herbal Practitioners to be effective in the management of cancer. The botanical families with the representation of more than one plant species were Fabaceae with five species, followed by Combretaceae and Anacardiaceae with tree species each and Meliaceaewith two species. The relative frequency of citation (RFC) showed that Senna singueana (RFC = 0.833), Lannea discolour (RFC = 0.833), Melia azedarach (RFC = 0.667), and Moringa oleifera (RFC = 0.667) were the medicinal plant species that were frequently mentioned and used in the study. The recipes could be a mixture of plant species or plant parts such as the leaves, barks, roots, rhizomes, seeds, flowers, and fruits. CONCLUSION The study showed that a potential cancer management drug could be developed from the medicinal plant species found in the area. The results of this study could provide baseline information on medicinal plant species for further phytochemical studies and other studies to validate their use.
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Affiliation(s)
| | - David Tembo
- Physics and Biochemical Sciences Department, The Polytechnic, University of Malawi, Blantyre, Malawi
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Ghosh S, Hazra J, Pal K, Nelson VK, Pal M. Prostate cancer: Therapeutic prospect with herbal medicine. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2021; 2:100034. [PMID: 34909665 PMCID: PMC8663990 DOI: 10.1016/j.crphar.2021.100034] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 05/10/2021] [Accepted: 05/12/2021] [Indexed: 12/12/2022] Open
Abstract
Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. A geographic variation on the burden of the disease suggested that the environment, genetic makeup, lifestyle, and food habits modulate one's susceptibility to the disease. Although it has been generally thought to be an older age disease, and awareness and timely execution of screening programs have managed to contain the disease in the older population over the last decades, the incidence is still increasing in the population younger than 50. Existing treatment is efficient for PCa that is localized and responsive to androgen. However, the androgen resistant and metastatic PCa are challenging to treat. Conventional radiation and chemotherapies are associated with severe side effects in addition to being exorbitantly expensive. Many isolated phytochemicals and extracts of plants used in traditional medicine are known for their safety and diverse healing properties, including many with varying levels of anti-PCa activities. Many of the phytochemicals discussed here, as shown by many laboratories, inhibit tumor cell growth and proliferation by interfering with the components in the pathways responsible for the enhanced proliferation, metabolism, angiogenesis, invasion, and metastasis in the prostate cells while upregulating the mechanisms of cell death and cell cycle arrest. Notably, many of these agents simultaneously target multiple cellular pathways. We analyzed the available literature and provided an update on this issue in this review article.
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Affiliation(s)
- Suvranil Ghosh
- Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India
| | - Joyita Hazra
- Department of Biotechnology, Indian Institute of Technology Madras, Tamil Nadu, India
| | | | - Vinod K. Nelson
- Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, Andhra Pradesh, India
| | - Mahadeb Pal
- Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India
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15
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Role of Herbal Teas in Regulating Cellular Homeostasis and Autophagy and Their Implications in Regulating Overall Health. Nutrients 2021; 13:nu13072162. [PMID: 34201882 PMCID: PMC8308238 DOI: 10.3390/nu13072162] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/19/2021] [Accepted: 06/20/2021] [Indexed: 02/06/2023] Open
Abstract
Tea is one of the most popular and widely consumed beverages worldwide, and possesses numerous potential health benefits. Herbal teas are well-known to contain an abundance of polyphenol antioxidants and other ingredients, thereby implicating protection and treatment against various ailments, and maintaining overall health in humans, although their mechanisms of action have not yet been fully identified. Autophagy is a conserved mechanism present in organisms that maintains basal cellular homeostasis and is essential in mediating the pathogenesis of several diseases, including cancer, type II diabetes, obesity, and Alzheimer’s disease. The increasing prevalence of these diseases, which could be attributed to the imbalance in the level of autophagy, presents a considerable challenge in the healthcare industry. Natural medicine stands as an effective, safe, and economical alternative in balancing autophagy and maintaining homeostasis. Tea is a part of the diet for many people, and it could mediate autophagy as well. Here, we aim to provide an updated overview of popular herbal teas’ health-promoting and disease healing properties and in-depth information on their relation to autophagy and its related signaling molecules. The present review sheds more light on the significance of herbal teas in regulating autophagy, thereby improving overall health.
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16
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The Effects of Dandelion Polysaccharides on Iron Metabolism by Regulating Hepcidin via JAK/STAT Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:7184760. [PMID: 33488942 PMCID: PMC7801049 DOI: 10.1155/2021/7184760] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 11/29/2020] [Accepted: 12/07/2020] [Indexed: 02/06/2023]
Abstract
Recent studies have claimed that iron overload was correlated with the risk of hepatocellular carcinoma (HCC), and our previous studies have also demonstrated that dandelion polysaccharide (DP) suppressed HCC cell line proliferation via causing cell cycle arrest and inhibiting the PI3K/AKT/mTOR pathway, but the effect of DP on metabolism is still not very clear. Here, we aim to clarify the effects of DP on iron metabolism and the underlying mechanism. In this study, we found that DP could reduce iron burden in hepatoma cells and grafted tumors. Hepcidin is a central regulator in iron metabolism. We confirmed that the expression of hepcidin in HCC tumor tissues was significantly higher than that in the adjacent nontumor tissues. The expression of hepcidin was downregulated in the liver of mouse model treatment with DP, as well as in hepatoma cells. Moreover, RNA sequencing and western blot data revealed that DP inhibited the IL-6-activated JAK-STAT signaling pathway. In summary, our results revealed that DP might be a new potential drug candidate for the regulation of iron burden and the treatment of HCC.
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Abd-Elhakim YM, Al-Sagheer AA. Opuntia spp. Benefits in Chronic Diseases. OPUNTIA SPP.: CHEMISTRY, BIOACTIVITY AND INDUSTRIAL APPLICATIONS 2021:423-455. [DOI: 10.1007/978-3-030-78444-7_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Scaria B, Sood S, Raad C, Khanafer J, Jayachandiran R, Pupulin A, Grewal S, Okoko M, Arora M, Miles L, Pandey S. Natural Health Products (NHP's) and Natural Compounds as Therapeutic Agents for the Treatment of Cancer; Mechanisms of Anti-Cancer Activity of Natural Compounds and Overall Trends. Int J Mol Sci 2020; 21:E8480. [PMID: 33187200 PMCID: PMC7697102 DOI: 10.3390/ijms21228480] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/08/2020] [Accepted: 11/09/2020] [Indexed: 12/12/2022] Open
Abstract
Most cancer therapeutics, such as tubulin-targeting chemotherapy drugs, cause cytotoxic, non-selective effects. These harmful side-effects drastically reduce the cancer patient's quality of life. Recently, researchers have focused their efforts on studying natural health products (NHP's) which have demonstrated the ability to selectively target cancer cells in cellular and animal models. However, the major hurdle of clinical validation remains. NHP's warrant further clinical investigation as a therapeutic option since they exhibit low toxicity, while retaining a selective effect. Additionally, they can sensitize cancerous cells to chemotherapy, which enhances the efficacy of chemotherapeutic drugs, indicating that they can be utilized as supplemental therapy. An additional area for further research is the investigation of drug-drug interactions between NHP's and chemotherapeutics. The objectives of this review are to report the most recent results from the field of anticancer NHP research, and to highlight the most recent advancements in possible supplemental therapeutic options.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Siyaram Pandey
- Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada; (B.S.); (S.S.); (C.R.); (J.K.); (R.J.); (A.P.); (S.G.); (M.O.); (M.A.); (L.M.)
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Medicinal Plants Used in Traditional Management of Cancer in Uganda: A Review of Ethnobotanical Surveys, Phytochemistry, and Anticancer Studies. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:3529081. [PMID: 32256639 PMCID: PMC7102457 DOI: 10.1155/2020/3529081] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 02/18/2020] [Indexed: 01/29/2023]
Abstract
The burden of neoplastic diseases is a significant global health challenge accounting for thousands of deaths. In Uganda, about 32,617 cancer cases were reported in 2018, accompanied by 21,829 deaths. In a view to identify some potential anticancer plant candidates for possible drug development, the current study was designed to compile the inventory of plants with reported anticancer activity used in rural Uganda and the evidences supporting their use in cancer therapy. An electronic survey in multidisciplinary databases revealed that 29 plant species belonging to 28 genera distributed among 24 families have been reported to be used in the management of cancer in Uganda. Anticancer plants were majorly from the families Bignoniaceae (7%), Caricaceae (7%), Fabaceae (7%), Moraceae (7%), and Rutaceae (7%). Most species occur in the wild (52%), though some are cultivated (48%). The growth habit of the plants is as trees (55%) or herbs (45%). Anticancer extracts are usually prepared from leaves (29%), bark (24%), roots (21%), and fruits (13%) through decoctions (53%), as food spices (23%) or pounded to produce ointments that are applied topically (10%). Prunus africana (Hook.f.) Kalkman, Opuntia species, Albizia coriaria (Welw. ex Oliver), Daucus carota L., Cyperus alatus (Nees) F. Muell., Markhamia lutea (Benth.) K. Schum., and Oxalis corniculata L. were the most frequently encountered species. As per global reports, Allium sativum L., Annona muricata L., Carica papaya L., Moringa oleifera Lam., Opuntia species, Prunus africana (Hook.f.) Kalkman, and Catharanthus roseus (L.) G. Don. are the most studied species, with the latter having vincristine and vinblastine anticancer drugs developed from it. Prostate, cervical, breast, and skin cancers are the top traditionally treated malignancies. There is a need to isolate and evaluate the anticancer potential of the bioactive compounds in the unstudied claimed plants, such as Cyperus alatus (Nees) F. Muell., Ficus dawei Hutch., Ficus natalensis Hochst., and Lovoa trichilioides Harms, and elucidate their mechanism of anticancer activity.
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Nassazi W, K’Owino I, Makatiani J, Wachira S. Phytochemical composition, antioxidant and antiproliferative activities of Rosmarinus officinalis leaves. FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY 2020. [DOI: 10.17721/fujcv8i2p150-167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Phytochemicals in Rosmarinus officinalis leaves, their total phenolic content, antioxidant potential and antiproliferative activity against human prostate (DU145), colon (CT26) and cervical (HeLa 229) cancer cells were investigated. Extraction was done separately using hexane, dichloromethane, ethyl acetate and methanol. A total of 32 compounds were identified, eight of which were reported for the first time. The highest phenolic content was 476.80 ± 0.69 µg/ml for the methanolic extract which also had the highest antioxidant activity with a minimum inhibitory concentration of 5.39 ± 0.09 mg/ml. Extracts exhibited the highest toxicity against prostate cancer cells and the least against cervical cancer cells.
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