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Xie X, Liao Y, Lin Z, Luo H, Wei G, Huang N, Li Y, Chen J, Su Z, Yu X, Chen L, Liu Y. Patchouli alcohol alleviates metabolic dysfunction-associated steatohepatitis via inhibiting mitochondria-associated endoplasmic reticulum membrane disruption-induced hepatic steatosis and inflammation in rats. Int Immunopharmacol 2024; 138:112634. [PMID: 38971107 DOI: 10.1016/j.intimp.2024.112634] [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: 03/19/2024] [Revised: 06/27/2024] [Accepted: 07/02/2024] [Indexed: 07/08/2024]
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is a severe metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by abnormal hepatic steatosis and inflammation. Previous studies have shown that Patchouli alcohol (PA), the primary component of Pogostemonis Herba, can alleviate digestive system diseases. However, its protection against MASH remains unclear. This study explored the protective effects and underlying mechanism of PA against high-fat diet-induced MASH in rats. Results showed that PA considerably reduced body weight, epididymal fat, and liver index and attenuated liver histological injury in MASH rats. PA alleviated hepatic injury by inhibiting steatosis and inflammation. These effects are associated with the improvement of SREBP-1c- and PPARα-mediated lipid metabolism and inhibition of the STING-signaling pathway-mediated inflammatory response. Moreover, PA-inhibited hepatic endoplasmic reticulum (ER) stress and mitochondrial dysfunction, reducing SREBP-1c and STING expressions and enhance PPARα expression. PA treatment had the strongest effect on the regulation of mitogen fusion protein 2 (Mfn2) in inhibiting mitochondrial dysfunction. Mfn2 is an important structural protein for binding ERs and mitochondria to form mitochondria-associated ER membranes (MAMs). MASH-mediated disruption of MAMs was inhibited after PA treatment-induced Mfn2 activation. Therefore, the pharmacological effect of PA on MASH is mainly attributed to the inhibition of MAM disruption-induced hepatic steatosis and inflammation. The findings of this study may have implications for MASH treatment that do not neglect the role of Mfn2-mediated MAMs.
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Affiliation(s)
- Xingyu Xie
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yingyi Liao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Zixin Lin
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Huijuan Luo
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau
| | - Guilan Wei
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Ning Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yucui Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, China
| | - Jiannan Chen
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Ziren Su
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Xiuting Yu
- Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, China; Pharmaceutical Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Liping Chen
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
| | - Yuhong Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, China.
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Chen H, Yang M, Shang X, Chen H, Li Y, Li Y, Li L, Qu M, Song X. Pogostemon cablin essential oil as feed additive promotes the repair of the rumen epithelial barrier in heat-stressed beef cattle. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 18:433-440. [PMID: 39309971 PMCID: PMC11416612 DOI: 10.1016/j.aninu.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/23/2024] [Accepted: 06/11/2024] [Indexed: 09/25/2024]
Abstract
Pogostemon cablin essential oil (PEO), extracted from P. cablin, has anti-oxidant, anti-inflammatory, and anti-stress properties, as well as the ability to improve gastrointestinal digestion. This study aims to evaluate the effects of PEO on the performance, rumen epithelial morphology, and barrier function in heat-stressed beef cattle. Thirty-six male Jingjiang cattle at 18 months old were randomly assigned into four groups and fed a diet containing PEO at 0 (control), 50, 100, or 150 mg/kg in the feed concentrate (n = 9). All experimental cattle were fed under high temperature and humidity in summer for 60 days. The results indicated that 50 mg/kg of PEO treatment enhanced the average daily gain of beef cattle compared with the control group (P = 0.032). All PEO treatments reduced the diamine oxidase activity (P = 0.004) and malondialdehyde content (P = 0.008) in serum. In addition, the content of 70 kDa heat shock protein in the 100 mg/kg group was increased, and the activity of glutathione peroxidase and total antioxidant capacity in both 100 mg/kg and 150 mg/kg groups were enhanced compared to the control group (P < 0.05). More importantly, PEO treatment with 50 mg/kg enhanced the mRNA relative expressions of occludin in ruminal epithelia but decreased the mRNA relative expressions of c-Jun N-terminal kinase, P38 mitogen-activated protein kinases, caspase-3, Beclin1 (P < 0.05), and extremely significant declined the mRNA relative expressions of extracellular regulated protein kinases and ubiquitin-binding protein in contrast to the control group (P < 0.01). These findings indicated that dietary PEO supplementation might be favorable to improve growth performance and repairing damaged rumen epithelium of heat-stressed cattle by down-regulating the mitogen-activated protein kinase signaling pathway.
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Affiliation(s)
| | | | - Xianglong Shang
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
| | - Hao Chen
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
| | - Yi Li
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
| | - Yanjiao Li
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
| | - Lin Li
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
| | - Mingren Qu
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
| | - Xiaozhen Song
- Jiangxi Province Key Laboratory of Animal Nutrition, Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang 330045, China
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Fang C, Zhang J, Han J, Lei Y, Cao Z, Pan J, Pan Z, Zhang Z, Qu N, Luo H, Ma Y, Han D. Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116838. [PMID: 37355081 DOI: 10.1016/j.jep.2023.116838] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/15/2023] [Accepted: 06/21/2023] [Indexed: 06/26/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. AIM OF THE STUDY To explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. MATERIAL AND METHODS 75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. RESULTS TJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. CONCLUSION According to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.
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Affiliation(s)
- Chunqiu Fang
- College of Pharmacy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Jingzhou Zhang
- First Affiliated Hospital, Changchun University of Chinese Medicine, Jilin, PR China
| | - Jiajun Han
- College of Pharmacy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Yuting Lei
- College of Pharmacy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Zhanhong Cao
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Jianheng Pan
- College of Pharmacy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Zhi Pan
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Zhong Zhang
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Jilin, PR China
| | - Ning Qu
- First Affiliated Hospital, Changchun University of Chinese Medicine, Jilin, PR China
| | - Haoming Luo
- College of Pharmacy, Changchun University of Chinese Medicine, Jilin, PR China.
| | - Yan Ma
- Department of Endocrinology and Metabolism, Jilin Province People's Hospital, Jilin, PR China.
| | - Dong Han
- College of Pharmacy, Changchun University of Chinese Medicine, Jilin, PR China.
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Lu DX, Liu F, Wu H, Liu HX, Chen BY, Yan J, Lu Y, Sun ZG. Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation. World J Gastroenterol 2022; 28:4574-4599. [PMID: 36157934 PMCID: PMC9476879 DOI: 10.3748/wjg.v28.i32.4574] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/05/2022] [Accepted: 07/18/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM).
AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.
METHODS We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed.
RESULTS WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1β, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid).
CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.
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Affiliation(s)
- Dong-Xue Lu
- Department of Nutrition, Acupuncture and Moxibustion and Massage College & Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Feng Liu
- Department of Orthopaedics, Nanjing Pukou District Chinese Medicine Hospital, Nanjing 210000, Jiangsu Province, China
| | - Hua Wu
- Department of Nutrition, Acupuncture and Moxibustion and Massage College & Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Hai-Xia Liu
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
| | - Bing-Yu Chen
- Department of Geriatrics, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 451150, Henan Province, China
| | - Jing Yan
- Key Laboratory for Metabolic Diseases in Chinese Medicine, The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Yin Lu
- Key Pharmacology Laboratory of Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Zhi-Guang Sun
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
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Xu L, Huang Q, Tan X, Zhao Q, Wu J, Liao H, Ai W, Liu Y, Lai Z, Fu L. Patchouli alcohol ameliorates acute liver injury via inhibiting oxidative stress and gut-origin LPS leakage in rats. Int Immunopharmacol 2021; 98:107897. [PMID: 34182243 DOI: 10.1016/j.intimp.2021.107897] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/26/2021] [Accepted: 06/14/2021] [Indexed: 12/16/2022]
Abstract
Alcoholism represents a predisposing factor for liver-related morbidity and mortality worldwide. Pogostemon cablin has been widely used in China for the treatment of digestive system diseases. Patchouli oil, the major active fraction of Pogostemon cablin, can ameliorate alcohol-induced acute liver injury (ALI). However, patchouli alcohol (PA),a principal bioactive ingredient of PO, exerts a protection against ALI remains elusive. Thepresentwork focused on the hepatoprotection of PA against acute ethanol-induced hepatotoxicity in rats. In this study, male Wistar rats orally received PA (10, 20, or 40 mg/kg), PO (400 mg/kg) and silymarin (200 mg/kg) for ten days. On the 8th day, the rats orally received 65% ethanol (10 mL/kg, 6.5 g/kg) every 12 h for 3 days. Results showed that PA wasfound to reduce alcohol-induced ALI, as evidenced bysignificantly alleviated histopathologicalalterations, decreased the elevation ofALT and AST levels, and enhancedthe alcoholdehydrogenase(ADH) andaldehyde dehydrogenase (ALDH) activities. Additionally, PA markedly suppressed ROS levels and increased antioxidant enzyme activities via the CYP2E1/ROS/Nrf2/HO-1 pathway. PA regulated lipid accumulation by markedly inhibiting the expression of lipogenesis-related genes and stimulating that of lipolysis-relatedgenes, which were associated with the activation of theAMPKpathway. What's more, PA pretreatment also restored acute alcohol-inducedalterationsin gut barrier function, colonic histopathology, and gut microbiota richness and evenness. PA pretreatment alleviated gut-origin LPS-inducedinflammation by inhibiting the MyD88/TLR4/NF-κB signal pathway. In general, PA ameliorates ethanol-induced ALI via restoration of CYP2E1/ROS/Nrf2/HO-1-mediatedoxidativestressand AMPK-mediated fat accumulation, as well as alleviation of gut-LPS-leakage-induced inflammation regulated by the MyD88/TLR4/NF-κB signaling pathway.
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Affiliation(s)
- Lieqiang Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Qionghui Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, PR China
| | - Xiaocui Tan
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Qian Zhao
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Jiazhen Wu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Huijun Liao
- Department of Clinical Pharmacy and Pharmaceutical services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated hospital of Shenzhen University), Shenzhen 518052, China
| | - Weipeng Ai
- Department of Pharmacy, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518055, PR China
| | - Yuhong Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Zhengquan Lai
- Department of Pharmacy, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518055, PR China.
| | - Ludi Fu
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
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Junren C, Xiaofang X, Mengting L, Qiuyun X, Gangmin L, Huiqiong Z, Guanru C, Xin X, Yanpeng Y, Fu P, Cheng P. Pharmacological activities and mechanisms of action of Pogostemon cablin Benth: a review. Chin Med 2021; 16:5. [PMID: 33413544 PMCID: PMC7791836 DOI: 10.1186/s13020-020-00413-y] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/18/2020] [Accepted: 12/11/2020] [Indexed: 02/07/2023] Open
Abstract
Patchouli ("Guanghuoxiang") or scientifically known as Pogostemon cablin Benth, belonging to the family Lamiaceae, has been used in traditional Chinse medicine (TCM) since the time of the Eastern Han dynasty. In TCM theory, patchouli can treat colds, nausea, fever, headache, and diarrhea. Various bioactive compounds have been identified in patchouli, including terpenoids, phytosterols, flavonoids, organic acids, lignins, glycosides, alcohols, pyrone, and aldehydes. Among the numerous compounds, patchouli alcohol, β-patchoulene, patchoulene epoxide, pogostone, and pachypodol are of great importance. The pharmacological impacts of these compounds include anti-peptic ulcer effect, antimicrobial effect, anti-oxidative effect, anti-inflammatory effect, effect on ischemia/reperfusion injury, analgesic effect, antitumor effect, antidiabetic effect, anti-hypertensive effect, immunoregulatory effect, and others.For this review, we examined publications from the previous five years collected from PubMed, Web of Science, Springer, and the Chinese National Knowledge Infrastructure databases. This review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies focused on clinical applications of this important plant extract.
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Affiliation(s)
- Chen Junren
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xie Xiaofang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Li Mengting
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xiong Qiuyun
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Li Gangmin
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Zhang Huiqiong
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Chen Guanru
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xu Xin
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Yin Yanpeng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Peng Fu
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China.
- West China School of Pharmacy, Sichuan University, 17 South Renmin Rd, 610065, Chengdu, China.
| | - Peng Cheng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China.
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 37 Shierqiao Road, Jinniu District, Chengdu, 611137, China.
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Xu N, Luo H, Li M, Wu J, Wu X, Chen L, Gan Y, Guan F, Li M, Su Z, Chen J, Liu Y. β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway. Biomed Pharmacother 2020; 134:111104. [PMID: 33341045 DOI: 10.1016/j.biopha.2020.111104] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 11/30/2020] [Accepted: 12/02/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been a leading cause of chronic metabolic disease, seriously posing healthy burdens to the public, whereas interventions available for it are limited to date. Patchouli oil had been reported to attenuate hepatic steatosis in our previous study. β-patchoulene (β-PAE) is a representative component separated from patchouli oil with multiple activities, but its effect against NAFLD is still unknown. To investigate the effect and potential mechanism of β-PAE on NAFLD, we used high fat diet (HFD) in vivo and free fatty acid (FFA) in vitro to induce hepatic steatosis in rats and L02 cells, respectively. Histological examination was evaluated via Hematoxylin-eosin and oil red O staining. The parameters for hepatic steatosis were estimated via biochemical kits, western blotting and quantitative real-time PCR. Compound C, the inhibitor of AMPK, was applied further to examine the precise mechanism of β-PAE on NAFLD. Our results indicated that β-PAE significantly attenuated HFD-induced weight gain, hepatic injury, lipid deposition in serum and hepatic tissue as well as FFA induced-lipid accumulation. Besides, β-PAE markedly improved the expression of AMP-activated protein kinase (AMPK) and its downstream factors which correlate with hepatic lipid synthesis and oxidation in vivo and in vitro. Nevertheless, Compound C abrogated the benefits derived from β-PAE in L02 cells. In conclusion, these results suggest that β-PAE exerts AMPK agonist-like effect to regulate hepatic lipid synthesis and oxidation, eventually prevent NAFLD progression.
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Affiliation(s)
- Nan Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Huijuan Luo
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Minyao Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Jiazhen Wu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Xue Wu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Liping Chen
- Faculty of Health Sciences, University of Macau, Macau, China
| | - Yuxuan Gan
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Fengkun Guan
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Mengyao Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Ziren Su
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan, 523808, China
| | - Jiannan Chen
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yuhong Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan, 523808, China.
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Liu Y, Wu J, Chen L, Wu X, Gan Y, Xu N, Li M, Luo H, Guan F, Su Z, Chen J, Li Y. β-patchoulene simultaneously ameliorated dextran sulfate sodium-induced colitis and secondary liver injury in mice via suppressing colonic leakage and flora imbalance. Biochem Pharmacol 2020; 182:114260. [PMID: 33017576 DOI: 10.1016/j.bcp.2020.114260] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 09/25/2020] [Accepted: 09/29/2020] [Indexed: 12/15/2022]
Abstract
Ulcerative colitis (UC) often occurs accompanied by colonic leakage and flora imbalance, resulting in secondary liver injury (SLI). SLI, in turn, aggravates UC, so the treatment of UC should not ignore it. β-patchoulene (β-PAE), a tricyclic sesquiterpene isolated from Pogostemon cablin, has been reported to exert a protective effect in gastrointestinal disease in our previous studies. However, its protection against UC and SLI remains unknown. Here we explored the protective effect and underlying mechanism of β-PAE against dextran sulfate sodium-induced UC and SLI in mice. The results indicated that β-PAE significantly reduced disease activity index, splenic index and attenuated the shortening of colonic length in UC mice. It alleviated colonic pathological changes and apoptosis through protecting tight junctions, reducing neutrophil aggregation, and inhibiting the release of pro-inflammatory cytokines and adhesion molecules. These effects of β-PAE were associated with the inhibition of TLR4/MyD88/NF-κB and ROCK1/MLC2 signalling pathway. UC-induced colonic leakage caused abnormally high LPS levels to result in SLI, and β-PAE markedly inhibited it. β-PAE simultaneously ameliorated SLI with reduced biomarker levels of endotoxin exposure and hepatic inflammation. High levels of LPS were also associated with flora imbalance in UC mice. However, β-PAE restored the diversity of gut microbiota and altered the relative abundance of characteristic flora of UC mice. Escherichia-dominated gut microbiota of UC mice was changed to Oscillospira-dominated after β-PAE treatment. In conclusion, pharmacological effects of β-PAE on UC and SLI were mainly contributed by suppressing colonic leakage and flora imbalance. The findings may have implications for UC treatment that not neglect the treatment of SLI.
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Affiliation(s)
- Yuhong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan 523808, China
| | - Jiazhen Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Liping Chen
- Faculty of Health Sciences, University of Macau, Macao, China
| | - Xue Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yuxuan Gan
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Nan Xu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Minyao Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Huijuan Luo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Fengkun Guan
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Department of Pharmacy, Central People's Hospital of Zhanjiang, Zhanjiang 524000, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan 523808, China
| | - Jiannan Chen
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
| | - Yucui Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
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Shin YK, Lee SY, Lee JM, Kang P, Seol GH. Effects of Short-Term Inhalation of Patchouli Oil on Professional Quality of Life and Stress Levels in Emergency Nurses: A Randomized Controlled Trial. J Altern Complement Med 2020; 26:1032-1038. [PMID: 32907352 DOI: 10.1089/acm.2020.0206] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Objectives: The aim of this study was to investigate the effects of patchouli (Pogostemon cablin Benth.) inhalation by emergency nurses on their stress, compassion satisfaction, compassion fatigue, burnout, blood pressure, and heart rate. Design: A randomized controlled trial. Setting/location: University hospital in Incheon. Subjects: This study was performed from May to August 2018 after all subjects provided written informed consent. Fifty eligible emergency nurses were recruited and randomly allocated to inhale 5% patchouli oil in sweet almond oil (patchouli group, n = 25) or pure sweet almond oil (control group, n = 25). Interventions: Nurses in the patchouli group first inhaled patchouli oil at about 10 pm (the end of an afternoon shift) and inhaled patchouli oil a second time at about 10 pm on next day (24-h interval). Nurses in the control group inhaled pure sweet almond oil following the same schedule. Outcome measures: Outcome measured included blood pressure, heart rate, levels of stress, compassion satisfaction, compassion fatigue, and burnout. Results: Although there were no significant differences in blood pressure, heart rate, compassion fatigue, and burnout, levels of stress were significantly lower (0.06 ± 0.48 vs. 1.19 ± 1.19, p < 0.001) and compassion satisfaction significantly higher (0.56 ± 2.50 vs. -2.84 ± 2.43, p < 0.001) in the patchouli than in the control group. In addition, relative to baseline, compassion fatigue was significantly lower in the patchouli group (26.72 ± 4.98 vs. 25.88 ± 4.63, p = 0.016). Conclusions: Inhalation of patchouli oil effectively reduced the levels of stress and increased compassion satisfaction in emergency nurses, suggesting that patchouli oil inhalation may improve the professional quality of life of emergency nurses. ClinicalTrials.gov ID: KCT0004615.
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Affiliation(s)
- You Kyoung Shin
- Department of Basic Nursing Science, College of Nursing, Korea University, Seoul, Republic of Korea
| | - So-Young Lee
- Department of Basic Nursing Science, College of Nursing, Korea University, Seoul, Republic of Korea
| | - Jeong-Min Lee
- KT&G Central Research Institute, Daejeon, Republic of Korea
| | - Purum Kang
- Department of Basic Nursing Science, College of Nursing, Korea University, Seoul, Republic of Korea.,Department of Nursing, College of Nursing, Woosuk University, Jeonju, Republic of Korea
| | - Geun Hee Seol
- Department of Basic Nursing Science, College of Nursing, Korea University, Seoul, Republic of Korea
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10
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Hong SJ, Cho J, Boo CG, Youn MY, Pan JH, Kim JK, Shin EC. Inhalation of Patchouli ( Pogostemon Cablin Benth.) Essential Oil Improved Metabolic Parameters in Obesity-Induced Sprague Dawley Rats. Nutrients 2020; 12:E2077. [PMID: 32668680 PMCID: PMC7400805 DOI: 10.3390/nu12072077] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/09/2020] [Accepted: 07/10/2020] [Indexed: 12/22/2022] Open
Abstract
This study investigated effects of patchouli essential oil (PEO) inhalation on metabolic parameters. First, to characterize aromatic compounds in PEO, solid-phase microextraction-gas chromatography/mass spectrometric detection was employed in which 19 aromatic compounds were identified. In GC-olfactometry analysis, linalool, α-patchoulene, and β-patchoulene were found to be the constituents exhibiting the highest similarity to the aromatic compounds in patchouli. In an animal experiment using Sprague Darley rats, groups with PEO inhalation had a reduced food intake compared to the control group. Additionally, body weight was lower in the obesity-induced animal model exposed to PEO inhalation than the group without PEO. However, we found no significant difference in organ weights between groups. In our serum analysis, high-density lipoprotein cholesterol was significantly higher in the PEO inhalation groups, while low-density lipoprotein cholesterol content was highest in the positive control group, suggesting that inhalation of the aromatic compounds present in patchouli may improve cholesterol profile. In addition, leptin levels were reduced in the groups treated with PEO inhalation, which explains the differences in food intake and body weight gains. Last, animal groups exposed to PEO inhalation showed a relatively lower systolic blood pressure which suggests that inhalation of PEO (or aromatic compounds therein) may assist in regulating blood pressure. Collectively, our data demonstrate that the inhalation of PEO influenced certain markers related to metabolic diseases, hence provide basic data for future research as to preventive/therapeutic applications of PEO as well as their aromatic constituents.
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Affiliation(s)
- Seong Jun Hong
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea; (S.J.H.); (J.C.); (C.G.B.); (M.Y.Y.)
| | - Jinju Cho
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea; (S.J.H.); (J.C.); (C.G.B.); (M.Y.Y.)
| | - Chang Guk Boo
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea; (S.J.H.); (J.C.); (C.G.B.); (M.Y.Y.)
| | - Moon Yeon Youn
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea; (S.J.H.); (J.C.); (C.G.B.); (M.Y.Y.)
| | - Jeong Hoon Pan
- Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE 19716, USA; (J.H.P.); (J.K.K.)
| | - Jae Kyeom Kim
- Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE 19716, USA; (J.H.P.); (J.K.K.)
| | - Eui-Cheol Shin
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea; (S.J.H.); (J.C.); (C.G.B.); (M.Y.Y.)
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11
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Gan Y, Ai G, Wu J, Luo H, Chen L, Huang Q, Wu X, Xu N, Li M, Su Z, Liu Y, Huang X. Patchouli oil ameliorates 5-fluorouracil-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport. JOURNAL OF ETHNOPHARMACOLOGY 2020; 250:112519. [PMID: 31883475 DOI: 10.1016/j.jep.2019.112519] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 09/26/2019] [Accepted: 12/24/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Pogostemon cablin, commonly named "Guang-Huo-Xiang" in China, has long been renowned for its ability to dispel dampness and regulate gastrointestinal functions. Patchouli oil (P.oil), the major active fraction of Pogostemon cablin, has been traditionally used as the principal component of Chinese medicinal formulae to treat exterior syndrome and diarrhea. However, the effects of P.oil in treating 5-fluorouracil (5-FU)-induced intestinal mucositis have not yet been reported. AIM OF THE STUDY To investigate the protective effects of P.oil against 5-FU-induced intestinal mucositis and the mechanisms underlying these effects. MATERIALS AND METHODS Sprague-Dawley rats were intraperitoneally injected with 5-FU (30 mg/kg) to establish an intestinal mucositis model. Meanwhile, rats with intestinal mucositis were orally administered with P.oil (25, 50, and 100 mg/kg). Histological analysis, ELISA (for detecting inflammatory cytokines and aquaporins), immunohistochemistry analysis (for examining caspases), qRT-PCR analysis (for assessment tight junctions), and western blotting analysis (for the assessment of TLR2/TLR4-MyD88 and VIP-cAMP-PKA signaling pathway-related proteins) were performed to estimate the protective effects of P.oil against intestinal mucositis and the mechanisms underlying these effects. RESULTS The histopathological assessment preliminarily exhibited that P.oil alleviated the 5-FU-induced damage to the intestinal structure. After P.oil administration, the elevation of the expression of cytokines (TNF-α, IFN-γ, and IL-13) decreased markedly and the activation of NF-κB and MAPK signaling was significantly inhibited. P.oil also increased the mRNA expression of ZO-1 and Occludin, thereby stabilizing intestinal barrier. In addition, P.oil decreased the expressions of caspase-8, caspase-3, and Bax, and increased the expression of Bcl-2, thereby reducing the apoptosis of the intestinal mucosa. These results were closely related to the regulation of the TLR2/TLR4-MyD88 signaling pathway. It has been indicated that P.oil possibly protected the intestinal barrier by reducing inflammation and apoptosis. Furthermore, this study showed that P.oil inhibited the abnormal expression of AQP3, AQP7, and AQP11 by regulating the VIP-cAMP-PKA signaling pathway. Furthermore, it restored the intestinal water absorption, thereby alleviating diarrhea. CONCLUSIONS P.oil ameliorated 5-FU-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.
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Affiliation(s)
- Yuxuan Gan
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Gaoxiang Ai
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Jiazhen Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Huijuan Luo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Liping Chen
- Faculty of Health Sciences, University of Macau, Macao, China
| | - Qionghui Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Xue Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Nan Xu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Minyao Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan, 523808, China
| | - Yuhong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Xiaoqi Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan, 523808, China.
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12
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Wu X, Xu N, Li M, Huang Q, Wu J, Gan Y, Chen L, Luo H, Li Y, Huang X, Su Z, Liu Y. Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats. Front Pharmacol 2019; 10:1134. [PMID: 31632274 PMCID: PMC6779828 DOI: 10.3389/fphar.2019.01134] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 09/02/2019] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.
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Affiliation(s)
- Xue Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Nan Xu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Minyao Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qionghui Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiazhen Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuxuan Gan
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liping Chen
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Huijuan Luo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yucui Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoqi Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuhong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
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13
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Wu C, Liu J, Tang Y, Li Y, Yan Q, Jiang Z. Hepatoprotective Potential of Partially Hydrolyzed Guar Gum against Acute Alcohol-Induced Liver Injury in Vitro and Vivo. Nutrients 2019; 11:E963. [PMID: 31035540 PMCID: PMC6567107 DOI: 10.3390/nu11050963] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/19/2019] [Accepted: 04/24/2019] [Indexed: 12/11/2022] Open
Abstract
Natural polysaccharides, particularly galactomannans, are potential candidates for treatment of alcoholic liver diseases (ALD). However, applications are restricted due to the physicochemical properties associated with the high molecular weight. In this work, guar gum galactomannans were partially hydrolyzed by β-mannanase, and the molecular mechanisms of hepatoprotective effects were elucidated both in vitro and in vivo. Release of lactate dehydrogenase and cytochrome C were attenuated by partially hydrolyzed guar gum (PHGG) in HepG2 cells, due to protected cell and mitochondrial membrane integrity. PHGG co-administration decreased serum amino transaminases and cholinesterase levels of acute alcohol intoxicated mice, while hepatic pathologic morphology was depleted. Activity of superoxide dismutase, catalase, and glutathione peroxidase was recovered to 198.2, 34.5, 236.0 U/mg protein, respectively, while malondialdehyde level was decreased by 76.3% (PHGG, 1000 mg/kg∙day). Co-administration of PHGG induced a 4.4-fold increment of p-AMPK expression, and lipid metabolism was mediated. PHGG alleviated toll-like-receptor-4-mediated inflammation via the signaling cascade of MyD88 and IκBα, decreasing cytokine production. Moreover, mediated expression of Bcl-2 and Bax was responsible for inhibited acute alcohol-induced apoptosis with suppressed cleavage of caspase 3 and PARP. Findings gained suggest that PHGG can be used as functional food supplement for the treatment of acute alcohol-induced liver injury.
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Affiliation(s)
- Chenxuan Wu
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100083, China.
| | - Jun Liu
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100083, China.
| | - Yanbin Tang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
| | - Yanxiao Li
- Bioresource Utilization Laboratory, College of Engineering, China Agricultural University, Beijing 100083, China.
| | - Qiaojuan Yan
- Bioresource Utilization Laboratory, College of Engineering, China Agricultural University, Beijing 100083, China.
| | - Zhengqiang Jiang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100083, China.
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