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Xiong Q, Li Z, Yang D, Liu X, Pu W, Yue X, Jia K, Wan X, Zou Y. Progress in the study of bioactivity, chemical composition and pharmacological mechanism of action in Wolfiporia cocos (F.A. Wolf) Ryvarden & Gilb. Front Pharmacol 2025; 16:1521235. [PMID: 40098611 PMCID: PMC11911342 DOI: 10.3389/fphar.2025.1521235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 02/06/2025] [Indexed: 03/19/2025] Open
Abstract
The Latin name of Wolfiporia cocos is Wolfiporia cocos (F.A. Wolf) Ryvarden & Gilb, it a medicinal and edible mushroom belonging to the family Polyporaceae. Traditional Chinese medicine believes that it can strengthen the spleen, diuretic, tranquillise the mind and dispel dampness. So far, the chemical and active metabolites isolated and extracted from Wolfiporia cocos are mainly polysaccharides, triterpenoids, and sterols. Modern pharmacology has found that these chemical and active metabolites have a wide range of pharmacological effects, including antitumour, antioxidation, anti-inflammatory, immunomodulation, regulation of intestinal flora, regulation of glycolipid metabolism, and improvement of organ function. By applying Poria cocos, Poria, Wolfiporia cocos, Wolfiporia cocos (F.A. Wolf) Ryvarden & Gilb as search terms, we searched all the relevant studies on Poria cocos from Web of Science and PubMed databases and classified these categories of chemical and active metabolites according to the main research content of each literature and summarized its mechanism of action, updated its latest research results, and discussed the direction of further research in the future to provide a better reference for future clinical applications with better therapeutic effects and potential medicinal value.
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Affiliation(s)
- Qi Xiong
- School of Medical Information, Changchun University of Chinese Medicine, Changchun, China
| | - Zhuoran Li
- School of Medical Information, Changchun University of Chinese Medicine, Changchun, China
| | - Defeng Yang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
| | - Xinze Liu
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China
| | - Wanxu Pu
- School of Medical Information, Changchun University of Chinese Medicine, Changchun, China
| | - Xitao Yue
- School of Medical Information, Changchun University of Chinese Medicine, Changchun, China
| | - Kaikai Jia
- School of Medical Information, Changchun University of Chinese Medicine, Changchun, China
| | - Xilin Wan
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China
- Jilin Aodong Pharmaceutial Group Co., Ltd., Post-Doctoral Research Center, Yanji, China
| | - Yuanjun Zou
- School of Medical Information, Changchun University of Chinese Medicine, Changchun, China
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Xie Z, Zeng H, He D, Luo J, Liu T, Shen B, Qin Y, Zhang S, Jin J. Insights into the inhibition of stomach cancer MKN45 cell growth by Poria cocos ethanol-soluble extract based on MAPK/PI3K signaling pathways and components cell fishing. JOURNAL OF ETHNOPHARMACOLOGY 2024; 320:117417. [PMID: 37977426 DOI: 10.1016/j.jep.2023.117417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/02/2023] [Accepted: 11/09/2023] [Indexed: 11/19/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Poria cocos F.A. Wolf is an edible fungus with forming sclerotia, which has the effects of promoting diuresis, exuding dampness, invigorating the spleen, and regulating the stomach. P. cocos has a high application in the clinic of traditional Chinese medicine, and some studies have indicated that P. cocos has a good effect on tumor diseases. According to ancient records and modern studies, P. cocos wine offers beneficial effects in terms of strengthening tendons and bones and anti-tumor effects. AIM OF THE STUDY To understand the substance composition of P. cocos ethanol-soluble extract (PESE) and then further study the effect and potential mechanism of PESE components on gastric cancer. MATERIALS AND METHODS In vitro and in vivo experiments were performed to detect the cell activity and apoptotic condition. Differential expression analysis and pathway enrichment were performed based on transcriptomics and were verified by real-time polymerase chain reaction and western blotting. The mice of the stomach cancer tumor model were randomly categorized into three groups. The weight and tumor volume of the mice were measured, and the pathological characteristics of tumor tissue and immunohistochemical changes were determined. Then, the main active components of PESE were detected by MKN45 cell fishing. RESULTS In vitro experiments showed that PESE inhibited the proliferation of MKN45 cells, but it did not induce apoptosis. Based on the transcriptome and western blotting results, the inhibition of MKN45 proliferation by PESE may be influenced by mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) signaling pathways. In vivo experiments showed that PESE inhibited tumor growth in mice and caused partial necrosis of tumor cells but had no toxic effect on mice. Cell fishing identified nine triterpenoids of P. cocos as the major active components of PESE. CONCLUSIONS The results indicated that PESE has a significant inhibitory effect on stomach cancer, and its mechanism probably commonly affects the MAPK and PI3K-Akt signaling pathways, which could be due to the triterpenoid components.
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Affiliation(s)
- Zhenni Xie
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China; Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, 410036, China
| | - Hongliang Zeng
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China; Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, 410036, China
| | - Dan He
- Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, 410036, China
| | - Ji Luo
- The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China
| | - Tingting Liu
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China
| | - Bingbing Shen
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China
| | - You Qin
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China
| | - Shuihan Zhang
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China; Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, 410036, China
| | - Jian Jin
- Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, China.
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Du YH, Zhao JJ, Li X, Huang SC, Ning N, Chen GQ, Yang Y, Nan Y, Yuan L. Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification. World J Gastrointest Oncol 2024; 16:30-50. [PMID: 38292852 PMCID: PMC10824110 DOI: 10.4251/wjgo.v16.i1.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 10/07/2023] [Accepted: 11/02/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear. AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification. METHODS The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis. RESULTS According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle. CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research.
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Affiliation(s)
- Yu-Hua Du
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Jian-Jun Zhao
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Xia Li
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Ningxia Chinese Medicine Research Center, Manufacturing Laboratory, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Shi-Cong Huang
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Na Ning
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Guo-Qing Chen
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Yang
- College of Foundation, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Nan
- Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
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Tarasiuk A, Mirocha G, Fichna J. Current status of Complementary and Alternative Medicine Interventions in the Management of Pancreatic Cancer - An Overview. Curr Treat Options Oncol 2023; 24:1852-1869. [PMID: 38079061 PMCID: PMC10781793 DOI: 10.1007/s11864-023-01146-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2023] [Indexed: 01/11/2024]
Abstract
OPINION STATEMENT Pancreatic cancer (PC) remains the deadliest cancer worldwide. Most patients are diagnosed at the advanced or metastatic stage, leading to a poor prognosis. Awareness of the limitations of current therapy and accompanying pain, depression, malnutrition, and side effects of chemoradiotherapy may lead patients and physicians towards complementary and alternative medicine (CAM). CAM refers to a diverse set of medical and healthcare practices, products, and systems that are not part of conventional Western medicine. Despite the low-quality evidence supporting the efficacy of these methods, they remain appealing due to patients' beliefs, fear of death, and the slow development of conventional therapy. Hence, the possibility of using natural products for pancreatic cancer is increasing. CAM options such as: medical cannabis, plants, fungi, herbal formulas, and injections, which originate primarily from traditional Chinese or Japanese medicine i.e. Curcuma longa, Panax ginseng, Poria cocos, Hochuekkito, Juzentaihoto, and Rikkunshito, Shi-quan-da-bu-tang/TJ-48, Huang-qin-tang, Shuangbai San, Wen Jing Zhi Tong Fang, Xiang-Sha-Liu-jun-zi-tang, Aidi injection, Brucea javanica oil emulsion/Yadanziyouru injection, Compound Kushen injection, Huachansu injection, Kangai injection and Kanglaite injections are becoming promising candidates for the management of pancreatic cancer. The abovementioned substances/medications are the most popular or potentially effective in PC treatment and consequently CAM-based adjuvant therapy through improving patients' quality of life, might be a useful addition in the treatment of pancreatic cancer patients.
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Affiliation(s)
- Aleksandra Tarasiuk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland.
| | - Grzegorz Mirocha
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland
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Son TH, Kim SH, Shin HL, Kim D, Huh JS, Ryoo R, Choi Y, Choi SW. Inhibition of Osteoclast Differentiation and Promotion of Osteogenic Formation by Wolfiporia extensa Mycelium. J Microbiol Biotechnol 2023; 33:1197-1205. [PMID: 37317624 PMCID: PMC10580891 DOI: 10.4014/jmb.2304.04048] [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: 12/12/2022] [Revised: 05/30/2023] [Accepted: 05/30/2023] [Indexed: 06/16/2023]
Abstract
Osteoporosis, Greek for "porous bone," is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as "Bokryung" in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.
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Affiliation(s)
- Tae Hyun Son
- School of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
- Forest Biomaterials Research Center, National Institute of Forest Science (NIFoS), Jinju 52817, Republic of Korea
| | - Shin-Hye Kim
- Forest Biomaterials Research Center, National Institute of Forest Science (NIFoS), Jinju 52817, Republic of Korea
| | - Hye-Lim Shin
- Forest Biomaterials Research Center, National Institute of Forest Science (NIFoS), Jinju 52817, Republic of Korea
| | - Dongsoo Kim
- Forest Biomaterials Research Center, National Institute of Forest Science (NIFoS), Jinju 52817, Republic of Korea
| | - Jin-Sung Huh
- Forest Biomaterials Research Center, National Institute of Forest Science (NIFoS), Jinju 52817, Republic of Korea
| | - Rhim Ryoo
- Forest Microbiology Division, Department of Forest Bio-Resources, NIFoS, Suwon 16631, Republic of Korea
| | - Yongseok Choi
- School of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
| | - Sik-Won Choi
- Forest Biomaterials Research Center, National Institute of Forest Science (NIFoS), Jinju 52817, Republic of Korea
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Jiang F, Zhu T, Yang C, Chen Y, Fu Z, Jiang L, Liu Y. Pachymic Acid Inhibits Growth and Metastatic Potential in Liver Cancer HepG2 and Huh7 Cells. Biol Pharm Bull 2023; 46:35-41. [PMID: 36273899 DOI: 10.1248/bpb.b22-00440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Pachymic acid (PA), exacted from Polyporaceae, has been known for its biological activities including diuretic, dormitive, anti-oxidant, anti-aging, anti-inflammatory and anticancer properties in several types of diseases. Recently, studies have demonstrated that PA could suppress cell growth and induce cell apoptosis in different kinds of cancer cells. But the underlying mechanisms remain poorly elucidated. In the current study, we investigated the effect of pachymic acid on liver cancer cells and its underlying mechanisms. Our results evidenced that pachymic acid effectively inhibited the cell growth and metastatic potential in HepG2 and Huh7 cells. Mechanistically, we revealed that pachymic acid triggered cell apoptosis by increasing caspase 3 and caspase 9 cleavage, upregulating Bax and cytochrome c expression, while reducing the expression of Bcl2. Besides, pachymic acid could markedly inhibit the cell invasion and migration and cell metastatic potential by mediating epithelial-to-mesenchymal transition (EMT) markers and metastasis-associated genes in HepG2 and Huh7 cells. In addition, we demonstrated that FAK-Src-Jun N-terminal kinase (JNK)-matrix metalloproteinase 2 (MMP2) axis was involved in PA-inhibited liver cell EMT. Together, these results contribute to our deeper understanding of the anti-cancer effects of pachymic acid on liver cancer cells. This study also provided compelling evidence that PA might be a potential therapeutic agent for liver cancer treatment.
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Affiliation(s)
- Feng Jiang
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
| | - Tieming Zhu
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
| | - Chunfeng Yang
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
| | - Yang Chen
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
| | - Zhidong Fu
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
| | - Lihui Jiang
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
| | - Yongzhi Liu
- Department of General Surgery, Affiliated Xiaoshan Hospital, Hangzhou Normal University
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Wei C, Wang H, Sun X, Bai Z, Wang J, Bai G, Yao Q, Xu Y, Zhang L. Pharmacological profiles and therapeutic applications of pachymic acid (Review). Exp Ther Med 2022; 24:547. [PMID: 35978941 PMCID: PMC9366251 DOI: 10.3892/etm.2022.11484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 06/17/2022] [Indexed: 01/10/2023] Open
Abstract
Poria cocos is a saprophytic fungus that grows in diverse species of Pinus. Its sclerotium, called fu-ling or hoelen, has been used in various traditional Chinese medicines and health foods for thousands of years, and in several modern proprietary traditional Chinese medicinal products. It has extensive clinical indications, including sedative, diuretic, and tonic effects. Pachymic acid (PA) is the main lanostane-type triterpenoid in Poria cocos. Evidence suggests that PA has various biological properties such as cytotoxic, anti-inflammatory, antihyperglycemic, antiviral, antibacterial, sedative-hypnotic, and anti-ischemia/reperfusion activities. Although considerable advancements have been made, some fundamental and intricate issues remain unclear, such as the underlying mechanisms of PA. The present study aimed to summarize the biological properties and therapeutic potential of PA. The biosynthetic, pharmacokinetic, and metabolic pathways of PA, and its underlying mechanisms were also comprehensively summarized.
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Affiliation(s)
- Chunyong Wei
- Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Hezhen Wang
- Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Xun Sun
- Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Zhixun Bai
- Department of Internal Medicine, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Jing Wang
- Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Guohui Bai
- Key Laboratory of Oral Disease Research, School of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Qizheng Yao
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Yingshu Xu
- Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Lei Zhang
- Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
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Xu J, Shen R, Jiao Z, Chen W, Peng D, Wang L, Yu N, Peng C, Cai B, Song H, Chen F, Liu B. Current Advancements in Antitumor Properties and Mechanisms of Medicinal Components in Edible Mushrooms. Nutrients 2022; 14:nu14132622. [PMID: 35807802 PMCID: PMC9268676 DOI: 10.3390/nu14132622] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/19/2022] [Accepted: 06/22/2022] [Indexed: 02/01/2023] Open
Abstract
Edible and medicinal fungi, a group of eukaryotic organisms with numerous varieties, including Coriolus versicolor, Ganoderma lucidum, Cordyceps sinensis, Pleurotus ostreatus, and Grifola frondosa, have been demonstrated to possess a board range of pharmaceutical properties, including anti-virus, anti-inflammation, and neuroprotection. Moreover, edible and medicinal fungi have been traditionally consumed as food to provide multiple nutrients and as drugs owing to having the activities of invigorating blood circulation, reinforcing the healthy qi, clearing away heat, and eliminating stasis for thousands of years in China. Malignant tumors, well-known as the second leading cause of death globally, accounted for nearly 10 million deaths in 2020. Thus, in-depth exploration of strategies to prevent and treat cancer is extremely urgent. A variety of studies have reported that the main bioactive components of edible and medicinal fungi, mainly polysaccharides and triterpenoids, exhibit diverse anticancer activities via multiple mechanisms, including inhibition of cell proliferation and metastasis, induction of apoptosis and autophagy, reversing multidrug resistance, and regulation of immune responses, thus suggesting their substantial potential in the prevention and treatment of cancer. Our review summarizes the research progress on the anticancer properties of edible and medicinal fungi and the underlying molecular mechanism, which may offer a better understanding of this field. Additionally, few studies have reported the safety and efficacy of extracts from edible and medicinal fungi, which may limit their clinical application. In summary, there is a need to continue to explore the use of those extracts and to further validate their safety and efficacy.
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Affiliation(s)
- Jing Xu
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Rui Shen
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Zhuoya Jiao
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Weidong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Daiyin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Lei Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Nianjun Yu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Can Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; (W.C.); (D.P.); (L.W.); (N.Y.); (C.P.)
| | - Biao Cai
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
| | - Hang Song
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
- Correspondence: (B.L.); (H.S.); (F.C.)
| | - Fengyuan Chen
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; (J.X.); (R.S.); (Z.J.); (B.C.)
- Correspondence: (B.L.); (H.S.); (F.C.)
| | - Bin Liu
- Cancer Research Center, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
- Correspondence: (B.L.); (H.S.); (F.C.)
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Chen HY, Lei JY, Li SL, Guo LQ, Lin JF, Wu GH, Lu J, Ye ZW. Progress in biological activities and biosynthesis of edible fungi terpenoids. Crit Rev Food Sci Nutr 2022; 63:7288-7310. [PMID: 35238261 DOI: 10.1080/10408398.2022.2045559] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The edible fungi have both edible and medicinal functions, in which terpenoids are one of the most important active ingredients. Terpenoids possess a wide range of biological activities and show great potential in the pharmaceutical and healthcare industries. In this review, the diverse biological activities of edible fungi terpenoids were summarized with emphasis on the mechanism of anti-cancer and anti-inflammation. Subsequently, this review focuses on advances in knowledge and understanding of the biosynthesis of terpenoids in edible fungi, especially in the generation of sesquiterpenes, diterpenes, and triterpenes. This paper is aim to provide an overview of biological functions and biosynthesis developed for utilizing the terpenoids in edible fungi.
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Affiliation(s)
- Hai-Ying Chen
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Jin-Yu Lei
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Shu-Li Li
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Li-Qiong Guo
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Jun-Fang Lin
- College of Food Science, South China Agricultural University, Guangzhou, China
| | - Guang-Hong Wu
- College of Food Science, South China Agricultural University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, China
| | - Jun Lu
- Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
| | - Zhi-Wei Ye
- College of Food Science, South China Agricultural University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, China
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Yijin-Tang Attenuates Cigarette Smoke and Lipopolysaccharide-Induced Chronic Obstructive Pulmonary Disease in Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7902920. [PMID: 35035511 PMCID: PMC8754600 DOI: 10.1155/2022/7902920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/17/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) refers to a lung disorder associated with symptoms of dyspnea, cough, and sputum production. Traditionally, Yijin-tang (YJT), a mixture of Pinellia ternate, Poria cocos, ginger, Chinese liquorice, and tangerine peel, has been prescribed for the treatment of respiratory system diseases caused by dampness phlegm. This experiment investigated the therapeutic effect of YJT in a mouse model of cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD. METHODS COPD was induced by exposing mice to CS for 1 hour per day for 8 weeks, with intranasal delivery of LPS on weeks 1, 3, 5, and 7. YJT was administered at doses of 100 and 200 mg/kg 1 hour before CS exposure for the last 4 weeks. RESULTS YJT significantly suppressed CS- and LPS-induced increases in inflammatory cell counts and reduced interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels in bronchoalveolar lavage fluid (BALF) and lung tissue. In addition, YJT not only decreased airway wall thickness, average alveolar intercept, and lung fibrosis, but it also suppressed the expression of matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-B (TGF-β) and collagen deposition. Moreover, YJT suppressed phosphorylation of nuclear factor-kappa B (NF-κB) as well as expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). CONCLUSION Collectively, our findings show that YJT attenuates respiratory inflammation and airway remodeling caused by CS and LPS exposure; therefore, therapeutic applications in COPD can be considered.
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Tu Y, Luo X, Liu D, Li H, Xia H, Ma C, Zhang D, Yang Y, Pan X, Wang T, Xia Y, Dan H, You P, Ye X. Extracts of Poria cocos improve functional dyspepsia via regulating brain-gut peptides, immunity and repairing of gastrointestinal mucosa. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 95:153875. [PMID: 34911003 DOI: 10.1016/j.phymed.2021.153875] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 11/12/2021] [Accepted: 11/29/2021] [Indexed: 05/13/2023]
Abstract
BACKGROUND Poria cocos (Schw.) Wolf (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. It has a very good therapeutic effect for functional dyspepsia (FD). However, the material basis and mechanism of PC on FD were not reported. PURPOSE To investigate the function and potential mechanisms of PC including its three extracts (triterpenoid, PCT; water-soluble polysaccharide, PCWP; acidic polysaccharide, PCAP) on FD. STUDY DESIGN The study explored the therapeutic effect of PC and its three extracts on FD in rats for the first time and discussed its mechanisms based on brain-gut peptides, immunity and repair of the gastrointestinal mucosa. METHODS The chemical components of PC extracts were analyzed and quantified using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and gel permeation chromatography coupled with size exclusion chromatography (GPC/SEC). The FD rat models were established using weight-loaded forced swimming and alternate-day fasting for 42 days. After 14 days of treatment, the effect and mechanisms were investigated using ELISA, histopathology, immunohistochemistry as well as Western blot. RESULTS Seventy-seven triterpenoids in PCT were identified. PCWP was primarily composed of component A (Mw: 3.831 × 107 Da), component B (Mw: 5.650 × 106 Da) and component C (Mw: 113,117 Da). PCAP was a homogeneous composition with an average Mw of 74,320 Da. PCT, PCWP and PCAP alleviated the symptoms of FD. These extracts promoted the repair of gastrointestinal mucosa and regulated the balance between the T helper cell (Th)1/Th2 axis and the Th17/Treg axis. PCT and PCWP regulated brain-gut peptides more effectively, PCWP and PCAP enhanced immunity more effectively. Further study demonstrated that these extracts may have enhanced immunity via the Toll-like receptor (TLR) and c-Jun N-terminal kinase (JNK) signaling pathways. CONCLUSIONS PC extracts showed therapeutic effects on FD rats, and the mechanism of action involved multiple pathways. PCAP, which is often discarded in traditional applications, was effective. Our study provides new ideas for the application and development of PC extracts.
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Affiliation(s)
- Yijun Tu
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Xinyao Luo
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Dan Liu
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Huijun Li
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Heyuan Xia
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Chaozhi Ma
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Dandan Zhang
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Yuying Yang
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Xiang Pan
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Tianhe Wang
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Yu Xia
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Hanxiong Dan
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China
| | - Pengtao You
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
| | - Xiaochuan Ye
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
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Tan W, Pan T, Wang S, Li P, Men Y, Tan R, Zhong Z, Wang Y. Immunometabolism modulation, a new trick of edible and medicinal plants in cancer treatment. Food Chem 2021; 376:131860. [PMID: 34971892 DOI: 10.1016/j.foodchem.2021.131860] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 10/04/2021] [Accepted: 12/10/2021] [Indexed: 12/23/2022]
Abstract
The edible and medicinal plants (EMPs) are becoming an abundant source for cancer prevention and treatment since the natural and healthy trend for modern human beings. Currently, there are more than one hundred species of EMPs widely used and listed by the national health commission of China, and most of them indicate immune or metabolic regulation potential in cancer treatment with numerous studies over the past two decades. In the present review, we focused on the metabolic influence in immunocytes and tumor microenvironment, including immune response, immunosuppressive factors and cancer cells, discussing the immunometabolic potential of EMPs in cancer treatment. There are more than five hundred references collected and analyzed through retrieving pharmacological studies deposited in PubMed by medical subject headings and the corresponding names derived from pharmacopoeia of China as a sole criterion. Finally, the immunometabolism modulation of EMPs was sketch out implying an immunometabolic control in cancer treatment.
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Affiliation(s)
- Wen Tan
- School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730000, China
| | - Tingrui Pan
- Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, Jiangsu 215123, China
| | - Shengpeng Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
| | - Peng Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
| | - Yongfan Men
- Research Laboratory of Biomedical Optics and Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China
| | - Rui Tan
- College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Zhangfeng Zhong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China.
| | - Yitao Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China.
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Gumbs AA, Spolverato G, Chouillard E. Integrative medicine and surgery: what are the diet and supplement recommendations for someone with pancreatic cancer? Hepatobiliary Surg Nutr 2021; 10:741-743. [PMID: 34760991 PMCID: PMC8527423 DOI: 10.21037/hbsn-20-863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 03/11/2021] [Indexed: 11/06/2022]
Affiliation(s)
- Andrew A. Gumbs
- Département de Chirurgie Digestive, Centre Hospitalier Intercommunal de Poissy/Saint-Germain-en-Laye, Poissy, France
- Grigol Robakidze University School of Medicine, T'bilisi, Republic of Georgia
| | - Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences, Hospital of the University of Padova, Padova, Italy
| | - Elie Chouillard
- Département de Chirurgie Digestive, Centre Hospitalier Intercommunal de Poissy/Saint-Germain-en-Laye, Poissy, France
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Zhang J, Guo H, Yan F, Yuan S, Li S, Zhu P, Chen W, Peng C, Peng D. An UPLC - Q - Orbitrap method for pharmacokinetics and tissue distribution of four triterpenoids in rats after oral administration of Poria cocos ethanol extracts. J Pharm Biomed Anal 2021; 203:114237. [PMID: 34242946 DOI: 10.1016/j.jpba.2021.114237] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 06/01/2021] [Accepted: 06/29/2021] [Indexed: 10/21/2022]
Abstract
Poria cocos (Schw.) Wolf, is a fungus that is widely used as medicine and dietary supplement in China. But its action mechanism is still not very clear. In this paper, a rapid, specific and sensitive high performace liquid chromatography coupled with hybrid quadrupole - orbitrap mass sepctrometry (UPLC - Q - Orbitrap MS) method has been developed and validated to simultaneously determine of four triterpenoids including Dehydrotumulosic acid (DTA), Dehydropachymic acid (DPA), Pachymic acid (PA), Dehydrotrametenolic acid (DMA) from Poria cocos in rat plasma and tissues. The analyte was extracted from rat plasma and tissue homogenates by protein precipitation with acetonitrile using glibenclamide as the internal standard (IS). Chromatographic separation was carried out on ACQUITY UPLC BEH - C18 column (2.1 mm × 50 mm, 1.7 μm) with a mobile phase composed of acetonitrile - water (containing 1.0 mmol/L ammonium acetate) using gradient elution at a flow rate of 0.2 mL/min. Electrospray ionization (ESI -) under negative ion mode was used, and its quantization was performed with multiple reaction monitoring (MRM) mode. The method was fully validated and successfully applied to pharmacokinetics and tissue distribution study in rats after oral administration of ethanol extracts of Poria cocos. Compared with that of plasma exporsure, triterpenoids could be detected in various tissues with a relatively high degree of tissue distribution. After oral administration, the concentration orders in seven different tissues were ranked as DTA > PA > DPA > DMA in intestine and stomach, wheras DTA > DMA > PA > DPA in heart, liver, spleen, lung and kidney tissues, which is speculated that DPA, PA may be converted into DMA in vivo. In conclusion, this results may provide a material basis for study of the pharmacological actions of triterpenoids in Poria cocos.
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Affiliation(s)
- Jing Zhang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China.
| | - Huimin Guo
- Center for Biological Technology, Anhui Agricultural University, Hefei, 230036, China
| | - Fulong Yan
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China
| | - Shujie Yuan
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China
| | - Siyu Li
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China
| | - Pengling Zhu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China
| | - Weidong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China; Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Hefei, 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China
| | - Can Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China; Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Hefei, 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China.
| | - Daiyin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China; Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Hefei, 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China.
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Chao CL, Huang HW, Su MH, Lin HC, Wu WM. The Lanostane Triterpenoids in Poria cocos Play Beneficial Roles in Immunoregulatory Activity. Life (Basel) 2021; 11:111. [PMID: 33535602 PMCID: PMC7912843 DOI: 10.3390/life11020111] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 12/11/2022] Open
Abstract
Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity.
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Affiliation(s)
- Chien-Liang Chao
- Sinphar Pharmaceutical Co., Ltd., Sinphar group, Yilan 269, Taiwan; (C.-L.C.); (H.-W.H.); (M.-H.S.)
| | - Hsin-Wen Huang
- Sinphar Pharmaceutical Co., Ltd., Sinphar group, Yilan 269, Taiwan; (C.-L.C.); (H.-W.H.); (M.-H.S.)
| | - Muh-Hwan Su
- Sinphar Pharmaceutical Co., Ltd., Sinphar group, Yilan 269, Taiwan; (C.-L.C.); (H.-W.H.); (M.-H.S.)
- School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
| | - Hang-Ching Lin
- Sinphar Pharmaceutical Co., Ltd., Sinphar group, Yilan 269, Taiwan; (C.-L.C.); (H.-W.H.); (M.-H.S.)
- School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
| | - Wen-Mein Wu
- Department of Nutritional Science, Fu-Jen Catholic University, Hsinchuang 24205, Taiwan
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16
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Jiang Y, Fan L. Evaluation of anticancer activities of Poria cocos ethanol extract in breast cancer: In vivo and in vitro, identification and mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2020; 257:112851. [PMID: 32283190 DOI: 10.1016/j.jep.2020.112851] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/30/2020] [Accepted: 04/04/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Poria cocos Wolf (P. cocos), a well-known traditional East-Asian medicinal and edible fungus, is one of the most important components in Chinese medicine formulas like "Guizhi fuling wan" to treat hyperplasia of mammary glands and breast cancer. AIMING OF STUDY In this study, we attempted to verify the anticancer efficacy of the ethanol extract of P. cocos (PC) on the breast cancer as well as to investigate its most active compound and its underlying molecular mechanism in vivo and in vitro. MATERIALS AND METHODS The key anti-cancer components were separated and purified through chromatography and identified by spectral analyses. The in vivo anti-breast cancer efficacy and side effects of PC were evaluated in BALB/c nude mice that have been subcutaneously injected with breast cancer cells MDA-MB-231. Cytotoxicity, apoptosis and cell cycle arrest of PC were evaluated in vitro by cell viability assays and flow cytometry. The protein levels were examined via western blotting. RESULTS Pachymic acid (PA), separated and identified as the most active compound, induced the significant cytotoxicity on breast cancer cells MDA-MB-231(IC50 value, 2.13 ± 0.24 μg/mL) and was not active against the normal breast epithelium cells MCF-10A. The in vivo experiment revealed that PC could significantly inhibit the tumor development and the final mean tumor weight of the mice in the PC group (0.51 ± 0.12g) was significantly lower than that in the model group (1.22 ± 0.45g). Notably, compared to the first-line anticancer drug cisplatin, PC showed less side effects on the function of the vital organs and the muscle strength of the mice. Among in vitro study, PC significantly inhibited the cell growth of MDA-MB-231 by inducing cell apoptosis and cell cycle arrested at G0/G1 phase in a dose-dependent manner. The expression of cell cycle-associated cyclin D1, cyclin E, CDK2, and CDK4 were downregulated, while p53 and p21 expression were upregulated following the PA treatment. In addition, PA downregulated the apoptotic regulator Bcl-2, increased the expression of pro-apoptotic protein Bax, and promoted the release of cytochrome c and the activation of cleaved caspase-3, -9 and caspase -8 via mitochondria-mediated and death receptor-mediated signaling pathways. CONCLUSION This study verified the anticancer efficacy of PC on breast cancer in vivo and in vitro through induction of cell apoptosis and G0/G1 cell cycle arrest. The data also suggested that PA could be developed as an efficacious agent for breast cancer treatment with less side effects.
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Affiliation(s)
- Yu Jiang
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Liuping Fan
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.
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Xu H, Wang Y, Zhao J, Jurutka PW, Huang D, Liu L, Zhang L, Wang S, Chen Y, Cheng S. Triterpenes from
Poria cocos
are revealed as potential retinoid X receptor selective agonists based on cell and in silico evidence. Chem Biol Drug Des 2020; 95:493-502. [DOI: 10.1111/cbdd.13610] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 07/11/2019] [Accepted: 08/11/2019] [Indexed: 01/17/2023]
Affiliation(s)
- Hui Xu
- Department of Food Quality and Safety School of Engineering China Pharmaceutical University Nanjing China
| | - Yuchen Wang
- Laboratory of Molecular Design and Drug Discovery School of Science China Pharmaceutical University Nanjing China
| | - Junnan Zhao
- Laboratory of Molecular Design and Drug Discovery School of Science China Pharmaceutical University Nanjing China
| | - Peter W. Jurutka
- School of Mathematical and Natural Sciences Arizona State University Phoenix AZ USA
| | - Dechun Huang
- Department of Pharmaceutical Engineering School of Engineering China Pharmaceutical University Nanjing China
| | - Liangyun Liu
- Department of Food Quality and Safety School of Engineering China Pharmaceutical University Nanjing China
| | - Lange Zhang
- Department of Food Quality and Safety School of Engineering China Pharmaceutical University Nanjing China
| | - Suilou Wang
- Department of Food Quality and Safety School of Engineering China Pharmaceutical University Nanjing China
| | - Yadong Chen
- Laboratory of Molecular Design and Drug Discovery School of Science China Pharmaceutical University Nanjing China
| | - Shujie Cheng
- Department of Food Quality and Safety School of Engineering China Pharmaceutical University Nanjing China
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Jana P, Acharya K. Mushroom: A New Resource for Anti-Angiogenic Therapeutics. FOOD REVIEWS INTERNATIONAL 2020. [DOI: 10.1080/87559129.2020.1721529] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Pradipta Jana
- Molecular and Applied Mycology and Pathology Laboratory, Department of Botany, University of Calcutta, Calcutta, India
| | - Krishnendu Acharya
- Molecular and Applied Mycology and Pathology Laboratory, Department of Botany, University of Calcutta, Calcutta, India
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Hasan UH, Uttra AM, Qasim S, Ikram J, Saleem M, Niazi ZR. Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflammation and rheumatoid arthritis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2020; 66:153134. [PMID: 31812101 DOI: 10.1016/j.phymed.2019.153134] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 10/26/2019] [Accepted: 11/07/2019] [Indexed: 06/10/2023]
Abstract
PURPOSE Matrix metalloproteinases, zinc dependent proteolytic enzymes, have significant implications in extracellular matrix degradation associated with tissue damage in inflammation and Rheumatoid arthritis. Numerous orchestrated pathways affects instigation and blockade of metalloproteinases as well as various factors that increase the expression of MMPs including inflammatory cytokines, hormones and growth factors. Direct inhibition of these proteolytic enzymes or modulation of these pathways can provide protection against tissue destruction in inflammation and rheumatoid arthritis. Inclination towards use of plant derived phytochemicals to prevent tissue damage has been increasing day by day. Diversity of phytochemicals have been known to directly inhibit metalloproteinases. Hence, thorough knowledge of phytochemicals is very important in novel drug discovery. METHODS Present communication evaluates various classes of phytochemicals, in effort to unveil the lead molecules as potential therapeutic agents, for prevention of MMPs mediated tissue damage in inflammation and rheumatoid arthritis. Data have been analyzed through different search engines. RESULTS Numerous phytochemicals have been studied for their role as MMPs inhibitors which can be processed further to develop into useful drugs for the treatment of inflammation and rheumatoid arthritis. CONCLUSION In search of new drugs, phytochemicals like flavonoids, glycosides, alkaloids, lignans & terpenes offer a wide canvas to develop into valuable forthcoming medicaments.
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Affiliation(s)
- Umme Habiba Hasan
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy University of Sargodha, Sargodha, Pakistan
| | - Ambreen Malik Uttra
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy University of Sargodha, Sargodha, Pakistan
| | - Sumera Qasim
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy University of Sargodha, Sargodha, Pakistan
| | - Javaria Ikram
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy University of Sargodha, Sargodha, Pakistan
| | - Muhammad Saleem
- University College of Pharmacy, University of Punjab Lahore, Lahore, Pakistan
| | - Zahid Rasul Niazi
- Department of Basic medical science, Faculty of Pharmacy, Gomal University, DI Khan, KPK, Pakistan
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Wang CC, Wang LK, Chen ML, Kuo CY, Tsai FM, Wang CH. Triterpenes in the Ethanol Extract of Poria cocos Induce Dermal Papilla Cell Proliferation. INT J PHARMACOL 2019. [DOI: 10.3923/ijp.2020.1.9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Xu H, Wang Y, Jurutka PW, Wu S, Chen Y, Cao C, Chen G, Tian B, Wang S, Cheng S. 16α-Hydroxytrametenolic Acid from Poria cocos Improves Intestinal Barrier Function Through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:10871-10879. [PMID: 31517482 DOI: 10.1021/acs.jafc.9b04613] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
This study evaluated the effect of triterpenoids from edible mushroom Poria cocos on intestinal epithelium integrity and revealed the transcriptional regulatory pathways that underpin restorative mechanisms in the gut. Based on computational docking studies, transcriptional activation experiments and glucocorticoid receptor (GR) protein immunofluorescence localization assays in cultured cells, 16α-hydroxytrametenolic acid (HTA) was discovered as a novel GR agonist in this study. HTA ameliorates TNF-α-induced Caco-2 monolayer intestinal epithelial barrier damage and suppressed activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), which attenuated downstream IκB and nuclear factor kappa-B (NF-κB) phosphorylation through GR activation. Moreover, HTA prevented NF-κB translocation into the nucleus and binding to its cis-element and suppressed lipopolysaccharide-induced downstream NO production and pro-inflammatory cytokines at both protein and mRNA expression levels. In conclusion, HTA from P. cocos improves intestinal barrier function through a GR-mediated PI3K/Akt/NF-κB signaling pathway and may be potentially exploited as a supportive dietary therapeutic strategy for restoring gut health.
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Affiliation(s)
- Hui Xu
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety/Key Laboratory of Grains and Oils Quality Control and Processing , Nanjing University of Finance and Economics , Nanjing 210023 , China
| | | | - Peter W Jurutka
- School of Mathematical and Natural Sciences , Arizona State University , Tempe , Arizona 85306 , United States
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Cheng S, Castillo V, Sliva D. CDC20 associated with cancer metastasis and novel mushroom‑derived CDC20 inhibitors with antimetastatic activity. Int J Oncol 2019; 54:2250-2256. [PMID: 31081056 DOI: 10.3892/ijo.2019.4791] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 03/26/2019] [Indexed: 11/06/2022] Open
Abstract
Aberrant expression of cell division cycle 20 (CDC20) is associated with malignant progression and poor prognosis in various types of cancer. The development of specific CDC20 inhibitors may be a novel strategy for the treatment of cancer with elevated expression of CDC20. The aim of the current study was to elucidate the role of CDC20 in cancer cell invasiveness and to identify novel natural inhibitors of CDC20. The authors found that CDC20 knockdown inhibited the migration of chemoresistant PANC‑1 pancreatic cancer cells and the metastatic MDA‑MB‑231 breast cancer cell line. By contrast, the overexpression of CDC20 by plasmid transfection promoted the metastasizing capacities of the PANC‑1 cells and MCF‑7 breast cancer cells. It was also identified that a triterpene mixture extracted from the mushroom Poria cocos (PTE), purified triterpenes dehydropachymic acid, and polyporenic acid C (PPAC) downregulated the expression of CDC20 in PANC‑1 cells dose‑dependently. Migration was also suppressed by PTE and PPAC in a dose‑dependent manner, which was consistent with expectations. Taken together, the present study is the first, to the best of our knowledge, to demonstrate that CDC20 serves an important role in cancer metastasis and that triterpenes from P. cocos inhibit the migration of pancreatic cancer cells associated with CDC20. Further investigations are in progress to investigate the specific mechanism associated with CDC20 and these triterpenes, which may have future potential use as natural agents in the treatment of metastatic cancer.
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Affiliation(s)
- Shujie Cheng
- Department of Food Quality and Safety, School of Engineering, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China
| | - Victor Castillo
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN 46202, USA
| | - Daniel Sliva
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN 46202, USA
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Wang Z, Qi F, Cui Y, Zhao L, Sun X, Tang W, Cai P. An update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics. Biosci Trends 2018; 12:220-239. [DOI: 10.5582/bst.2018.01144] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Zhixue Wang
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
| | - Fanghua Qi
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
| | - Yangang Cui
- Department of Chemotherapy, Shandong Provincial Hospital affiliated to Shandong University
| | - Lin Zhao
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
| | - Xiaogang Sun
- Department of Tumor Minimally Invasive Surgery, Shandong Provincial Hospital affiliated to Shandong University
| | - Wei Tang
- National Center for Global Health and Medicine
| | - Pingping Cai
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
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Sun KX, Xia HW. Pachymic acid inhibits growth and induces cell cycle arrest and apoptosis in gastric cancer SGC-7901 cells. Oncol Lett 2018; 16:2517-2524. [PMID: 30013646 DOI: 10.3892/ol.2018.8899] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Accepted: 12/19/2017] [Indexed: 12/28/2022] Open
Abstract
The aim of the present study was to elucidate the anticancer effect of pachymic acid (PA) in gastric cancer SGC-7901 cells and the potential molecular mechanisms involved. Cell Count kit-8 assay was performed to examine the effect of PA on the cell proliferation of SGC-7901 cells. Cell cycle, cell apoptosis, mitochondria membrane potential (Dψm) and reactive oxygen species (ROS) analysis were assessed by flow cytometry, respectively. DNA fragmentation assay was performed by Hoechst 33258 staining. Western blotting was performed to detect the effect of various concentrations of PA on the levels of BCL2 associated X protein (Bax) expression as well as B-cell lymphoma 2 (Bcl-2), cytochrome C (cyt-c) and caspase-3 in SGC-7901 cells. It was demonstrated that PA was able to significantly inhibit the viability and induce G0/G1 cell cycle arrest of SGC-7901 cells in a concentration-dependent manner. The apoptotic rate and ROS generation were markedly increased, while Dψm was decreased following the treatment of SGC-7901 cells with various concentrations of PA. Moreover, the expression of Bax, cytochrome c and caspase-3 were markedly increased and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was significantly inactivated and BCL-2 expression was decreased following PA treatment in SGC-7901 cells. Notably, JAK2 inhibitor (AG490) mimics the effects of PA on the viability and apoptosis of SGC-7901 cells. Further in vivo study indicated that treatment with PA significantly inhibited the growth of tumor in nude mice that were transplanted with SGC-7901 cells in a concentration-dependent manner. These results may advance the current understanding of the anticancer mechanisms of PA in gastric cancer.
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Affiliation(s)
- Kuan-Xue Sun
- Department of General Surgery, Gong Li Hospital of Shanghai Pu Dong New District, Shanghai 200135, P.R. China.,Department of Ultrasound, Gong Li Hospital of Shanghai Pu Dong New District, Shanghai 200135, P.R. China
| | - Hong-Wei Xia
- Department of Ultrasound, Gong Li Hospital of Shanghai Pu Dong New District, Shanghai 200135, P.R. China
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Molecular mechanism of Poria cocos combined with oxaliplatin on the inhibition of epithelial-mesenchymal transition in gastric cancer cells. Biomed Pharmacother 2018; 102:865-873. [PMID: 29710543 DOI: 10.1016/j.biopha.2018.03.134] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 03/21/2018] [Accepted: 03/22/2018] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Natural product Poria cocos possesses antitumor effect. This study will explore the molecular mechanism of Poria cocos combined with chemotherapy in the inhibition of gastric cancer cell EMT process. METHODS The experiment was divided into blank control group, Poria cocos group, oxaliplatin group and Poria cocos combined with oxaliplatin group. Scratch and Transwell assay were used to detect cell migration and invasion respectively. RT-qPCR and Western Blot analyses were used to detect mRNA and protein expression of the epithelial-mesenchymal transition (EMT) related factors including Snail, Twist, Vimentin, E-cadherin and N-cadherin respectively. Morphologic assessment was performed with HPIAS-1000 automated image analysis system. RESULTS The migration and invasion abilities of gastric cancer cells in the Poria cocos combined with oxaliplatin group were significantly decreased (P < 0.01). The mRNA and protein expression of Snail, Twist, Vimentin and N-cadherin were significantly decreased while the mRNA and protein expression of E-cadherin were significantly increased (P < 0.01) compared with blank control group. Nude mice model of gastric cancer was successfully established. Poria cocos combined with oxaliplatin could significantly inhibit gastric tumor progression. The expression of EMT related factors were consistent with in vitro study. Morphologic assessment showed that the nucleus area, perimeter, mean diameter, volume, long diameter and shape factor in the Poria cocos combined with oxaliplatin group were significantly different compared with the blank control group (P < 0.01) but not significantly different compared with the normal control. CONCLUSIONS Poria cocos combined with oxaliplatin could significantly inhibit the migration and invasion of gastric cancer cells. Through both in vitro and in vivo studies, it is confirmed that Poria cocos combined with oxaliplatin could significantly inhibit the EMT process of gastric cancer. Poria cocos combined with oxaliplatin could significantly affect the morphology changes of gastric cancer cells. These findings may provide a theoretical guidance for the clinical treatment of gastric cancer.
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Jiao L, Dong C, Liu J, Chen Z, Zhang L, Xu J, Shen X, Che J, Yang Y, Huang H, Li H, Sun J, Jiang Y, Mao Z, Chen P, Gong Y, Jin X, Xu L. Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients. Sci Rep 2017; 7:46524. [PMID: 28436479 PMCID: PMC5402288 DOI: 10.1038/srep46524] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 03/22/2017] [Indexed: 01/05/2023] Open
Abstract
The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens.
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Affiliation(s)
- Lijing Jiao
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
| | - Changsheng Dong
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jiaxiang Liu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
| | - Zhiwei Chen
- Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China
| | - Lei Zhang
- Department of Thoracic surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China
| | - Jianfang Xu
- Departmentof Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China
| | - Xiaoyong Shen
- Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Jiaming Che
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, China
| | - Yi Yang
- Department of Thoracic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai 200030, China
| | - Hai Huang
- Department of Pneumology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China
| | - Hegen Li
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jianli Sun
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yi Jiang
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Zhujun Mao
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Peiqi Chen
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yabin Gong
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
| | - Xiaolin Jin
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
| | - Ling Xu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
- Tumor Institute of Traditional Chinese Medicine, Shanghai Research Institute of Traditional Chinese Medicine, Shanghai 200032, China
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
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Zhang YH, Zhang Y, Li XY, Feng XD, Jian W, Li RQ. Antitumor activity of the pachymic acid in nasopharyngeal carcinoma cells. Ultrastruct Pathol 2017; 41:245-251. [PMID: 28414554 DOI: 10.1080/01913123.2017.1296522] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Yan-Hua Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
| | - Yong Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
| | - Xiu-Ying Li
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
| | - Xu-Dong Feng
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
| | - Wei Jian
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
| | - Rong-Qing Li
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
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Li S, Zhang J, Li S, Liu C, Liu S, Liu Z. Extraction and separation of lactate dehydrogenase inhibitors from Poria cocos (Schw.) Wolf based on a hyphenated technique and in vitro methods. J Sep Sci 2017; 40:1773-1783. [PMID: 28217983 DOI: 10.1002/jssc.201700054] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 02/05/2017] [Accepted: 02/09/2017] [Indexed: 12/20/2022]
Abstract
Stroke is one of the most common diseases worldwide. Lactate dehydrogenase inhibitors are widely used in the treatment of ischemic stroke, with natural products considered a promising source of lactate dehydrogenase inhibitors. In this study, ultrafiltration liquid chromatography coupled with mass spectrometry was used for the screening and identification of lactate dehydrogenase inhibitors from Poria cocos. Five lactate dehydrogenase inhibitors were selected: dehydropachymic acid, pachymic acid, dehydrotrametenolic acid, trametenolic acid, and eburicoic acid. The inhibitors were extracted and isolated with purities of 96.75, 98.15, 97.25, 95.46, and 94.88%, respectively, by using a new "hyphenated" strategy of microwave-assisted extraction coupled with counter-current chromatography and centrifugal partition chromatography by a two-phase solvent system of n-hexane/ethyl acetate/ethanol/water at the volume ratio 0.965:1.000:0.936:0.826 v/v/v/v. The bioactivity of the isolated compounds was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in PC12 cells. The results also showed that the hyphenated technique of microwave-assisted extraction coupled with counter-current chromatography and centrifugal partition chromatography was an efficient method for the continuous extraction and online isolation of chemical constituents from medicinal herbs. Furthermore, the research route based on the activity screening, extraction, separation, and activity verification of the compounds offered advantages of efficiency, orientation, and objectivity.
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Affiliation(s)
- Sainan Li
- Central Laboratory, Changchun Normal University, Changchun, China.,Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
| | - Jianxu Zhang
- Department of Rehabilitation, Second Branch of the First Hospital of Jilin University, Changchun, China
| | - Senlin Li
- Central Laboratory, Changchun Normal University, Changchun, China
| | - Chunming Liu
- Central Laboratory, Changchun Normal University, Changchun, China
| | - Shu Liu
- Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
| | - Zhiqiang Liu
- Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
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Cheng S, Castillo V, Welty M, Alvarado M, Eliaz I, Temm CJ, Sandusky GE, Sliva D. BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:115. [PMID: 28209156 PMCID: PMC5314617 DOI: 10.1186/s12906-017-1621-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 02/02/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. METHODS Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry. RESULTS Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer. CONCLUSION BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.
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DNA Microarray-Based Screening and Characterization of Traditional Chinese Medicine. MICROARRAYS 2017; 6:microarrays6010004. [PMID: 28146102 PMCID: PMC5374364 DOI: 10.3390/microarrays6010004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 01/23/2017] [Indexed: 12/14/2022]
Abstract
The application of DNA microarray assay (DMA) has entered a new era owing to recent innovations in omics technologies. This review summarizes recent applications of DMA-based gene expression profiling by focusing on the screening and characterizationof traditional Chinese medicine. First, herbs, mushrooms, and dietary plants analyzed by DMA along with their effective components and their biological/physiological effects are summarized and discussed by examining their comprehensive list and a list of representative effective chemicals. Second, the mechanisms of action of traditional Chinese medicine are summarized by examining the genes and pathways responsible for the action, the cell functions involved in the action, and the activities found by DMA (silent estrogens). Third, applications of DMA for traditional Chinese medicine are discussed by examining reported examples and new protocols for its use in quality control. Further innovations in the signaling pathway based evaluation of beneficial effects and the assessment of potential risks of traditional Chinese medicine are expected, just as are observed in other closely related fields, such as the therapeutic, environmental, nutritional, and pharmacological fields.
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An ethanol extract of Poria cocos inhibits the proliferation of non-small cell lung cancer A549 cells via the mitochondria-mediated caspase activation pathway. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.03.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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Yang HJ, Yim NH, Lee KJ, Gu MJ, Lee B, Hwang YH, Ma JY. Simultaneous determination of nine bioactive compounds in Yijin-tang via high-performance liquid chromatography and liquid chromatography-electrospray ionization-mass spectrometry. Integr Med Res 2016; 5:140-150. [PMID: 28462109 PMCID: PMC5381425 DOI: 10.1016/j.imr.2016.04.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 03/30/2016] [Accepted: 04/07/2016] [Indexed: 01/18/2023] Open
Abstract
Background Yijin-tang (YJ) has been used traditionally for the treatment of cardiovascular conditions, nausea, vomiting, gastroduodenal ulcers, and chronic gastritis. In this study, a simple and sensitive high-performance liquid chromatography (HPLC) method was developed for the quantitation of nine bioactive compounds in YJ: homogentisic acid, liquiritin, naringin, hesperidin, neohesperidin, liquiritigenin, glycyrrhizin, 6-gingerol, and pachymic acid. Methods Chromatographic separation of the analytes was achieved on an RS Tech C18 column (4.6 mm × 250 mm, 5 μm) using a mobile phase composed of water containing 0.1% (v/v) trifluoroacetic acid (TFA) and acetonitrile with a gradient elution at a flow rate of 1.0 mL/min. Results Calibration curves for all analytes showed good linearity (R2 ≥ 0.9995). Lower limits of detection and lower limits of quantification were in the ranges of 0.03–0.17 μg/mL and 0.09–0.43 μg/mL, respectively. Relative standard deviations (RSDs; %) for intra- and interday assays were < 3%. The recovery of components ranged from 98.09% to 103.78%, with RSDs (%) values ranging from 0.10% to 2.59%. Conclusion This validated HPLC method was applied to qualitative and quantitative analyses of nine bioactive compounds in YJ and fermented YJ, and may be a useful tool for the quality control of YJ.
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Affiliation(s)
- Hye Jin Yang
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
| | - Nam-Hui Yim
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
| | - Kwang Jin Lee
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
| | - Min Jung Gu
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
| | - Bohyoung Lee
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
| | - Youn-Hwan Hwang
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
| | - Jin Yeul Ma
- KM Application Center, Korea Institute of Oriental Medicine, Daegu, Korea
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Qi F, Zhao L, Zhou A, Zhang B, Li A, Wang Z, Han J. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends 2015; 9:16-34. [PMID: 25787906 DOI: 10.5582/bst.2015.01019] [Citation(s) in RCA: 308] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Recent studies indicate that Traditional Chinese medicine (TCM) can play an important role in the whole course of cancer treatment such as recovery stages of post-operative, radiotherapy or chemotherapy stages instead of only terminal stage of cancer. In this review, we have summarized current evidence for using TCM as adjuvant cancer treatment in different stages of cancer lesions. Some TCMs (e.g., TJ-41, Liu-jun-zi-tang, PHY906, Coumarin, and Aescine) are capable of improving the post-operative symptoms such as fatigue, pain, appetite, diarrhea, nausea, vomiting, and lymphedema. Some TCMs (e.g., Ginseng, Huang-Qi, BanZhiLian, TJ-48, Huachansu injection, Shenqi fuzheng injection, and Kanglaite injection) in combination with chemo- or radio-therapy are capable of enhancing the efficacy of and diminishing the side effects and complications caused by chemo- and radiotherapy. Taken together, they have great advantages in terms of suppressing tumor progression, relieving surgery complications, increasing the sensitivity of chemo- and radio- therapeutics, improving an organism's immune system function, and lessening the damage caused by surgery, chemo- or radio-therapeutics. They have significant effects on relieving breast cancer-related lymphedema, reducing cancer-related fatigue and pain, improving radiation pneumonitis and gastrointestinal side effects, protecting liver function, and even ameliorating bone marrow suppression. This review of those medicines should contribute to an understanding of Chinese herbal medicines as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer, by providing useful information for development of more effective anti-cancer drugs and making more patients "survival with cancer" for a long time.
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Affiliation(s)
- Fanghua Qi
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
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Jiang WG, Sanders AJ, Katoh M, Ungefroren H, Gieseler F, Prince M, Thompson SK, Zollo M, Spano D, Dhawan P, Sliva D, Subbarayan PR, Sarkar M, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Ye L, Helferich WG, Yang X, Boosani CS, Guha G, Ciriolo MR, Aquilano K, Chen S, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Nowsheen S, Pantano F, Santini D. Tissue invasion and metastasis: Molecular, biological and clinical perspectives. Semin Cancer Biol 2015; 35 Suppl:S244-S275. [PMID: 25865774 DOI: 10.1016/j.semcancer.2015.03.008] [Citation(s) in RCA: 351] [Impact Index Per Article: 35.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 03/17/2015] [Accepted: 03/18/2015] [Indexed: 12/12/2022]
Abstract
Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.
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Affiliation(s)
- W G Jiang
- Cardiff University, Cardiff, United Kingdom.
| | | | - M Katoh
- National Cancer Center, Tokyo, Japan
| | - H Ungefroren
- University Hospital Schleswig-Holstein, Lübeck, Germany
| | - F Gieseler
- University Hospital Schleswig-Holstein, Lübeck, Germany
| | - M Prince
- University of Michigan, Ann Arbor, MI, USA
| | | | - M Zollo
- Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples Federico II, Naples, Italy; CEINGE Biotecnologie Avanzate, Naples, Italy
| | - D Spano
- CEINGE Biotecnologie Avanzate, Naples, Italy
| | - P Dhawan
- University of Nebraska Medical Center, Omaha, USA
| | - D Sliva
- Purdue Research Park, Indianapolis, IN, USA
| | | | - M Sarkar
- University of Miami, Miami, FL, USA
| | - K Honoki
- Nara Medical University, Kashihara, Japan
| | - H Fujii
- Nara Medical University, Kashihara, Japan
| | - A G Georgakilas
- Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - A Amedei
- University of Florence, Florence, Italy
| | | | - A Amin
- United Arab Emirates University, Al Ain, United Arab Emirates and Faculty of Science, Cairo University, Egypt
| | - S S Ashraf
- United Arab Emirates University, Al Ain, United Arab Emirates and Faculty of Science, Cairo University, Egypt
| | - L Ye
- Cardiff University, Cardiff, United Kingdom
| | - W G Helferich
- University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - X Yang
- University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | | | - G Guha
- SASTRA University, Thanjavur, India
| | | | - K Aquilano
- University of Rome Tor Vergata, Rome, Italy
| | - S Chen
- Ovarian and Prostate Cancer Research Trust Laboratory, Surrey, United Kingdom
| | - A S Azmi
- Wayne State University, Detroit, MI, USA
| | - W N Keith
- University of Glasgow, Glasgow, United Kingdom
| | - A Bilsland
- University of Glasgow, Glasgow, United Kingdom
| | - D Bhakta
- SASTRA University, Thanjavur, India
| | - D Halicka
- New York Medical College, Valhalla, NY, USA
| | - S Nowsheen
- Mayo Clinic College of Medicine, Rochester, MN, USA
| | - F Pantano
- University Campus Bio-Medico, Rome, Italy
| | - D Santini
- University Campus Bio-Medico, Rome, Italy
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An elderly patient with advanced lung cancer achieved long-term survival using Chinese medicine: An alternative treatment strategy for cancer patients aged 80 or older without a tissue confirmed diagnosis. Chin J Integr Med 2015; 22:545-8. [DOI: 10.1007/s11655-015-2309-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Indexed: 11/28/2022]
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Chen Y, Lian P, Liu Y, Xu K. Pachymic acid inhibits tumorigenesis in gallbladder carcinoma cells. Int J Clin Exp Med 2015; 8:17781-17788. [PMID: 26770369 PMCID: PMC4694269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 10/08/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. Thus, seeking targets gallbladder tumor cells is an attractive goal towards improving clinical treatment. MATERIAL AND METHODS In this study, we investigated the effects of pachymic acid (PA) on the tumorigenesis of human gallbladder cancer cells. RESULTS We found that PA significantly reduced cell growth in a dose- and time-dependent fashion. Meanwhile, cell cycle arrest at G0 phase was induced by PA. PA also significantly inhibited cancer cell migration, invasion in a dose-dependent manner. Interestingly, we demonstrated that cancer cell adhesion ability was suppressed dose-dependently, which may contribute to the inhibition of cell invasion. Finally, we showed that PA inhibited AKT and ERK signaling pathways. And oncoproteins, such as PCNA, ICAM-1 and RhoA which are involved intumorigenesis, were also downregulated by PA. CONCLUSION Our study reveals that PA is able to inhibit gallbladder cancer tumorigenesis involving affection of AKT and ERK signaling pathways. Together, these results encourage further studies of PA as a promising candidate for gallbladder cancer therapy.
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Affiliation(s)
- Yueguang Chen
- Department of General Surgery, Qilu Hospital, Shandong University Jinan 250012, P. R. China
| | - Peilong Lian
- Department of General Surgery, Qilu Hospital, Shandong University Jinan 250012, P. R. China
| | - Yanfeng Liu
- Department of General Surgery, Qilu Hospital, Shandong University Jinan 250012, P. R. China
| | - Kesen Xu
- Department of General Surgery, Qilu Hospital, Shandong University Jinan 250012, P. R. China
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Choi YH. Induction of apoptosis by an ethanol extract of Poria cocos Wolf. in human leukemia U937 cells. Oncol Rep 2015; 34:2533-40. [PMID: 26353048 DOI: 10.3892/or.2015.4256] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Accepted: 07/31/2015] [Indexed: 11/06/2022] Open
Abstract
Poria cocos Wolf., which belongs to the Polyporaceae family, has been widely used as an Oriental traditional herbal medicine for centuries. Its sclerotium has been reported to possess a wide spectrum of pharmacological activities, including free-radical scavenging, anti-viral, anti-microbial, anti-inflammatory and anticancer activities. However, the cellular and molecular mechanisms of apoptosis induction by P. cocos in human cancer cells are poorly understood. In the present study, we investigated the pro-apoptotic potential of an ethanol extract of P. cocos sclerotium (EEPC) in human leukemia U937 cells in vitro. We found that EEPC induced anti-proliferative effects in U937 cells in a concentration- and time-dependent manner, which was due to apoptotic induction, as evident from morphological changes and flow cytometric assays. EEPC-induced apoptosis of U937 cells was associated with an increase in the Bax:Bcl-2 ratio, the release of cytochrome c to the cytosol, and a decrease in the expression of an inhibitor of the apoptosis family of proteins. The events were accompanied by activation of caspase-8, -9 and -3, and cleaved poly(ADP-ribose) polymerase, suggesting the involvement of both the intrinsic and extrinsic apoptotic cascades. In addition, the overexpression of Bcl-2 caused a significant attenuation of EEPC-induced caspase activation, degradation of PARP, and the collapse of mitochondrial membrane potential, and thereby reversed EEPC-induced cell apoptosis and growth inhibition. Collectively, these data provide insights into the molecular mechanisms underlying EEPC-induced apoptosis in U937 cells, suggesting that EEPC may be a new therapeutic option for the treatment of leukemia.
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Affiliation(s)
- Yung Hyun Choi
- Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea
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Cheng S, Swanson K, Eliaz I, McClintick JN, Sandusky GE, Sliva D. Pachymic acid inhibits growth and induces apoptosis of pancreatic cancer in vitro and in vivo by targeting ER stress. PLoS One 2015; 10:e0122270. [PMID: 25915041 PMCID: PMC4411097 DOI: 10.1371/journal.pone.0122270] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 02/12/2015] [Indexed: 12/17/2022] Open
Abstract
Pachymic acid (PA) is a purified triterpene extracted from medicinal fungus Poria cocos. In this paper, we investigated the anticancer effect of PA on human chemotherapy resistant pancreatic cancer. PA triggered apoptosis in gemcitabine-resistant pancreatic cancer cells PANC-1 and MIA PaCa-2. Comparative gene expression array analysis demonstrated that endoplasmic reticulum (ER) stress was induced by PA through activation of heat shock response and unfolded protein response related genes. Induced ER stress was confirmed by increasing expression of XBP-1s, ATF4, Hsp70, CHOP and phospho-eIF2α. Moreover, ER stress inhibitor tauroursodeoxycholic acid (TUDCA) blocked PA induced apoptosis. In addition, 25 mg kg-1 of PA significantly suppressed MIA PaCa-2 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, growth inhibition and induction of apoptosis by PA in gemcitabine-resistant pancreatic cancer cells were associated with ER stress activation both in vitro and in vivo. PA may be potentially exploited for the use in treatment of chemotherapy resistant pancreatic cancer.
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Affiliation(s)
- Shujie Cheng
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America
| | - Kristen Swanson
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America
| | - Isaac Eliaz
- Amitabha Medical Clinic and Healing Center, Santa Rosa, California, United States of America
| | - Jeanette N. McClintick
- Departments of Biochemistry and Molecular Biology, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America
| | - George E. Sandusky
- Departments of Pathology, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America
| | - Daniel Sliva
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America
- Departments of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America
- DSTest Laboratories, Purdue Research Park, Indianapolis, Indiana, United States of America
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Cheng S, Castillo V, Eliaz I, Sliva D. Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R signaling. Int J Oncol 2015; 46:2293-8. [PMID: 25846316 PMCID: PMC4441299 DOI: 10.3892/ijo.2015.2950] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 02/10/2015] [Indexed: 01/01/2023] Open
Abstract
Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis.
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Affiliation(s)
- Shujie Cheng
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA
| | - Victor Castillo
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA
| | - Isaac Eliaz
- Amitabha Medical Clinic and Healing Center, Santa Rosa, CA, USA
| | - Daniel Sliva
- Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA
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Han JC, Li XD, Du J, Xu F, Wei YJ, Li HB, Zhang YJ. Elevated matrix metalloproteinase-7 expression promotes metastasis in human lung carcinoma. World J Surg Oncol 2015; 13:5. [PMID: 25588786 PMCID: PMC4326471 DOI: 10.1186/1477-7819-13-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 12/03/2014] [Indexed: 01/11/2023] Open
Abstract
Background Matrix metalloproteinase 7 (MMP-7) promotes tumor invasion and metastasis in several cancers. However, its role in lung cancer progression is understudied. In this study, we investigated the correlation between MMP-7 expression and lung cancer pathology. Methods We searched the databases PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, China BioMedicine (CBM) and China National Knowledge Infrastructure (CNKI) for scientific literature relevant to MMP-7 and lung cancer. Carefully selected studies were pooled and ORs with 95% CI were calculated. Subgroup analyses and publication bias were analyzed to understand the retrieved data in greater detail. Version 12.0 STATA software was used for statistical analysis. Results We retrieved a total of 121 studies through database searches. Finally, 14 cohort studies satisfied our inclusion/exclusion criteria, and these 14 studies, published between 2004 and 2012, were selected for meta-analysis to understand the influence of MMP-7 expression in lung cancer progression. Our results showed consistent differences in MMP-7 expression when comparisons were made between TNM I-II versus III-IV (OR = 1.82, 95% CI: 1.19 to 2.78, P = 0.006); histologic grade 1 to 2 versus 3 to 4 (OR = 1.67, 95% CI: 1.14 to 2.42, P = 0.008); and lymph node-negative versus lymph node-positive samples (OR = 2.81, 95% CI: 1.73 to 4.58, P <0.001), with significantly higher MMP-7 expression levels found in the more advanced stages. Subgroup analysis showed that age was not the factor influencing the associations between histologic grade, LN metastasis and MMP-7 expression in lung cancer patients, as both under 60 and over 60 age groups showed strong correlations (all P <0.05). However, when TNM staging was analyzed for its association with MMP-7 expression, only patients under age 60 showed a statistically significant correlation. Conclusions Our meta-analysis results revealed that MMP-7 overexpression is associated with advanced TNM and histological grades, and is linked to aggressive LN metastasis in lung cancer patients; thus MMP-7 is a useful biomarker to assess the disease status in lung cancers.
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Affiliation(s)
| | | | | | | | | | | | - Yi-Jie Zhang
- Department of Respiration, Huaihe Hospital of Henan University, Ximen Street No, 115, Kaifeng 475000, P,R China.
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Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2015; 863:95-116. [DOI: 10.1007/978-3-319-18365-7_5] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Xing XJ, Gu XH, Ma TF. Relationship of serum MMP-7 levels for colorectal cancer: a meta-analysis. Tumour Biol 2014; 35:10515-22. [PMID: 25060179 DOI: 10.1007/s13277-014-2349-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 07/13/2014] [Indexed: 12/16/2022] Open
Abstract
This meta-analysis aimed to identify the value of serum matrix metalloproteinase-7 (MMP-7) levels for the diagnosis of colorectal cancer (CRC). Through searching the following electronic databases: Cochrane Library (Issue 12, 2014), Web of Science (1945∼2014), PubMed (1966∼2014), CINAHL (1982∼2014), EMBASE (1980∼2014), and CBM (1982∼2014), related articles were determined without any language restrictions. Stata statistical software (Version 12.0, Stata Corporation, College Station, TX, USA) was chosen to deal with statistical data. Standard mean difference (SMD) and its corresponding 95 % confidence interval (95 % CI) were calculated to clarify the correlation between serum MMP-7 levels and CRC. Seven clinical case-control studies which recruited 430 CRC patients and 357 healthy subjects were selected for statistical analysis. The main findings of our meta-analysis showed that the serum MMP-7 level in CRC patients was significantly higher than that in control subjects (SMD = 2.15, 95 % CI = 1.46∼2.84, P < 0.001). Ethnicity-stratified analysis indicated a higher serum MMP-7 level in CRC patients than that of control subjects among the Asians and the Caucasians (Asians: SMD = 2.83, 95 % CI = 1.76∼3.91, P < 0.001; Caucasians: SMD = 1.06, 95 % CI = 0.46∼1.66, P = 0.001; respectively). The present meta-analysis indicated that the increased serum level of MMP-7 may be connected with the development of CRC; thus, serum levels of MMP-7 could be an independent biomarker for CRC patients.
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Affiliation(s)
- Xiao-Jing Xing
- Department of Internal Oncology, Liaoning Cancer Hospital and Institute, No. 44, Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People's Republic of China,
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Pan S, Hu J, Zheng T, Liu X, Ju Y, Xu C. Oleanolic acid derivatives induce apoptosis in human leukemia K562 cell involved in inhibition of both Akt1 translocation and pAkt1 expression. Cytotechnology 2014; 67:821-9. [PMID: 24728886 DOI: 10.1007/s10616-014-9722-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 03/20/2014] [Indexed: 12/12/2022] Open
Abstract
Oleanolic acid (OA) derivatives exhibit numerous pleiotropic effects in many cancers. The present study aimed to investigate the molecular mechanisms of 5'-amino-oleana-2,12-dieno[3,2-d]pyrimidin-28-oic acid (compound 4) and oleana-2,12-dieno[2,3-d]isoxazol-28-oic acid (compound 5) inducing apoptosis in human leukemia K562 cell. We investigated the effects of the compounds on K562 cell growth, apoptosis and cell cycle. The compounds showed strong inhibitory effects on K562 cell viability in a dose-dependent manner determined by the 3-(4,5-dimethylthiazoyl)-2,5-diphenyltetrazolium bromide assay and significantly increased chromatin condensation and apoptotic bodies in K562 cells. Flow cytometry assay suggested that the compounds induced inhibition of K562 cell proliferation associated with G1 phase arrest. In addition, the compounds inhibited Akt1 recruiting to membrane in CHO cells which express Akt1-EGFP constitutively and down-regulated the expression of pAkt1 in K562 cell. These results suggested that the compounds can efficiently inhibit proliferation and induce apoptosis perhaps involved in inactivation of Akt1. The OA derivatives may be potential chemotherapeutic agents for the treatment of human cancer.
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Affiliation(s)
- Shuhua Pan
- College of Life Science, Zhejiang Sci-Tech University, Xiasha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, China
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Jeong JW, Lee HH, Han MH, Kim GY, Hong SH, Park C, Choi YH. Ethanol extract of Poria cocos reduces the production of inflammatory mediators by suppressing the NF-kappaB signaling pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 14:101. [PMID: 24628870 PMCID: PMC3985596 DOI: 10.1186/1472-6882-14-101] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Accepted: 03/10/2014] [Indexed: 12/21/2022]
Abstract
Background Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined. Methods In the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC’s effect on the nuclear factor-kappaB (NF-κB) signaling pathway. Results Our results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC’s inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC’s inhibitory effects on inhibitor kappaB (IκB) degradation. Conclusions Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.
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