• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    The advances of traditional Chinese medicine in the treatment of liver diseases in 2019

    2020-06-29 07:43:28MinCaoJingMiaoLiWangHaiZhaoLiuHuanTianCuiYuHongBian
    Traditional Medicine Research 2020年4期

    Min Cao, Jing Miao, Li Wang, Hai-Zhao Liu, Huan-Tian Cui, Yu-Hong Bian

    The advances of traditional Chinese medicine in the treatment of liver diseases in 2019

    Min Cao1#, Jing Miao2#, Li Wang3, Hai-Zhao Liu1, Huan-Tian Cui4, Yu-Hong Bian5*

    1Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;2Department of Integrated Traditional and Western Medicine, Tianjin Second People’s Hospital, Tianjin 300192, China;3Department of Pharmacy, Tianjin Second People’s Hospital, Tianjin 300192, China;4Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 250100, China;5College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

    Currently, the treatment of liver diseases remains an unsolved problem due to its complicated etiology and pathogenesis. Traditional Chinese medicine (TCM) has been used for liver disease treatment for thousands of years. Disease treatment using TCM compounds conforms to the concept of “holism”, which coincides with the complicated pathogenic mechanisms of liver diseases. However, the mechanisms have not been clearly explained due to the complex components and multi-targets, which is a big obstacle TCM’s popularity and application. In recent years, studying the mechanisms and identifying the novel ingredients in herbal medicines are becoming a hot spot for many researchers. Therefore, we obtained literature in PubMed and summarized the progress of TCM’s active ingredients and formulas in treating various liver diseases in 2019. Based on the literature, flavonoids, polysaccharides, saponins, and alkaloids, as well as Chinese medicine formulas, such as Ba-Bao pill and Yin-Chen-Hao decoction, have attracted much attention. In addition, we also focused on the application of new omics analysis techniques, such as metabolomics, network pharmacology, and other omics analyses in the study of TCM formulas.

    Traditional Chinese medicine, Liver diseases, Mechanism, Metabolomics, Network pharmacology, Omics analysis

    This article focuses on introducing the mechanism and application prospect of the active ingredients and formulas of traditional Chinese medicine in the treatment of liver diseases in 2019. Metabolomics, transcriptomics, network pharmacology, 16S rRNA gene sequencing, and other omic analyses have been widely used in many studies in the past year.

    This annual review summarizes the hot research mechanisms of traditional Chinese medicine in the treatment of liver disease, especially hepatitis, liver injury, non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma in 2019, which can provide a comprehensive description of the hot spots and ongoing research areas.

    Background

    Liver diseases, mainly including hepatitis, liver injury, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and hepatocellular carcinoma (HCC), have become a global threat for human health due to their high global prevalence rate and poor prognosis [1]. Currently, less effective medicines have been developed to control the progression of these liver diseases. Most patients need to receive lifelong medications, increasing the economic burden of the patients and their families. Moreover, long-term medication may cause hepatotoxicity and renal toxicity, which could exacerbate the liver damage and impair renal functions [2]. Therefore, identifying more effective, safer, and cheaper medicines for liver disease treatment is becoming a necessary research focus.

    Traditional Chinese medicine (TCM) has been used on liver diseases for thousands of years. However, the mechanisms have not been clearly explained due to the multi-compounds and multi-targets, which is a big obstacle for the wide use of TCM worldwide. Studying the mechanisms and identifying the novel ingredients could promote Chinese herbal medicine application. In addition, novel techniques such as metabolomics, network pharmacology, and other omics analyses have also been applied in this field. In 2019, the accumulated effort of researchers made great advances in studying the possible mechanisms of TCM on liver diseases.

    In this review, we summarized the research progress of several studies on the active ingredients and formulas in treating liver diseases. Papers focusing on TCM usage in liver diseases in PubMed were searched, with “l(fā)iver disease” and “traditional Chinese medicine” as the keywords. Generally, more than 700 articles were obtained from January 1, 2019 to December 31, 2019 in PubMed. We analyzed the number of literature published in different countries in 2019 via PubReMiner (https://hgserver2.amc.nl/cgi-bin/miner/miner2.cgi), a tool enabling the counting of the occurrence of certain search results within PubMed Search [3]. China contributed 679 papers in this field (Figure 1). Then, we summarized the top ten journals according to the number of published articles. Most of the articles were from the, which published 48 papers in 2019 (Figure 2). Moreover, we found that liver injury, NAFLD, liver fibrosis, and HCC were the mainly studied liver diseases (Figure 3).

    Figure 1 An analysis of the number of articles regarding the use of TCM in the treatment of liver diseases published in different countries in 2019. We searched in PubReMiner (https://hgserver2.amc.nl/cgi-bin/miner/miner2.cgi) using the keywords “l(fā)iver disease” and “traditional Chinese medicine” from 2019/01/01 to 2019/12/31 and analyzed the country distribution of the resulted articles.

    Figure 2 The top 10 journals with publications of TCM in the treatment of liver diseases in 2019. We searched in the PubReMiner (https://hgserver2.amc.nl/cgi-bin/miner/miner2.cgi) using the keywords “l(fā)iver disease” and “traditional Chinese medicine” from 2019/01/01 to 2019/12/31 to analyze the journal’s contribution.

    Figure 3 The top 12 keywords in TCM on liver disease therapy in 2019. We searched in the PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) database using the keywords “l(fā)iver disease” and “traditional Chinese medicine” from 2019/01/01 to 2019/12/31 to analyze the keyword contribution.

    Hepatitis

    Hepatitis B and C virus (HBV and HCV, respectively) are the major risk factors of liver injury, liver cirrhosis, and HCC. Currently, interferon and nucleoside (acid) analogs are the first-line clinical HBV and HCV treatment medicines. However, the covalently closed circular DNA of HBV could not be eliminated completely, and long-term medication could induce side effects, such as nephrotoxicity, bone toxicity, and medicine resistance [4–5]. Clinical studies also indicated that many patients experienced recurring HBV and HCV infection after medicine withdrawal [6–7]. In 2019, several articles showed that Chinese herbs and formulas could inhibit viral replication and control hepatitis progression. The saponins extracted from Jigucao (Hance) could inhibit the DNA replication of HBV by increasing the CD4+/CD3+T cell ratio and promoting interferon (IFN)-γ secretion [5]. Empirical formulas, especially the Bushen formula, consist of Huangqi (), Nüzhenzi (Lucidi), Yinyanghuo (Maxim), Huhuanglian (), and Qingpi (), which could significantly decrease the levels of Hepatitis B surface antigen in patients with HBV, compared with entecavir treatment alone. It also showed that the regulatory T cell number and the PD-L1 expression in dendritic cells were decreased in HBV-infected patients after the combination treatment with Bushen formula and entecavir[8]. The classical prescription Yin-Chen-Hao decoction, first described in the ancient book of Chinese medicine(), is composed of 18 g of Yinchen (), 12 g of Zhizi (), and 6 g of Dahuang (.), which could improve the clinical effect of patients with HBV [7]. In addition, a survey in Taiwan compared the effects and prognosis of patients with HCV that were treated with or without TCM, such as Danshen () and Huzhang (), and found that Chinese herbal medicine, as an adjuvant treatment, reduced the total mortality of patients and lowered the risk of cirrhosis and hepatoma development [9].

    Liver injury

    Liver injury is usually caused by exogenous substances, such as alcohol, medicines, and chemicals, which could cause liver metabolism disorders, oxidative stress, and toxification [10]. Nuclear factor 2-related factor 2 (Nrf2) is an important transcription factor of a series of detoxification and antioxidant defense genes in the liver, which plays an important role in protecting the liver against oxidative injury. Several TCMs have been proven to activate Nrf2-related signaling pathways and their downstream key antioxidant enzymes to protect against liver injuries in 2019 [11–12].

    Acute liver injury

    Quercetin is a naturally occurring polyphenolic flavonoid with a great antioxidant capacity and is commonly found in Huangqi ((Fisch.) Bunge.) [13], tomatoes, and berries [14], which could attenuate toosendanin-induced acute liver injury by promoting the Nrf2-GCL-GSH antioxidant signaling pathway [11]. Magnolol, the main chemical component ofHoupo (), could prevent alcohol-induced acute liver injury by activating the PI3K-Nrf2-peroxisome proliferator-activated receptor (PPAR)γ signaling pathway and inhibiting NOD-like receptor protein 3 inflammasome [15]. Chinese patent drug Ba-Bao pill (SFDA approval number of China: Z10940006) consists of eight constituents, including natural Niuhuang (), Shedan (snake gall), Lingyangjiao (), Shexiang (), and Sanqi (), which protected against acute ethanol-induced liver injury in mice by activating the Nrf2 pathway to decrease hepatocyte oxidative stress [16]. In addition, metabolomics and 16S rRNA gene sequencing indicated that the classical prescription Yin-Chen-Hao decoction, first described in the ancient book of Chinese medicine(), could prevent carbon tetrachloride (CCL4)-induced acute liver injury by regulating 3-hydroxybutyric acid production andandratios in the gut [17].

    Chronic liver injury

    Hot water extracts of Zhijuzi (), including 1.08% dihydromyricetin, 0.43% dihydroquercetin, and 1.40% quercetin, could alleviate lipid deposition and inflammation response in ethanol-induced chronic liver injury by modulating abnormalities in the gut-liver axis and inhibiting the TLR4 pathway [18]. A set prescription of the Tibetan medicine San-Wei-Gan-Jiang powder, first described in the(–), is composed of three herbs, including Ganjiang (Rosc.), Caodoukou (AHayat), and Roudoukou (), which could protect against CCL4-induced chronic liver injury in rats by dynamically regulating the Nrf2–Bach1 pathway [19]. The empirical formula “Compound T11” contains 14 Chinese medicines, including Huzhang (Sieb. et Zucc.), Sharen (Lour.), Dahuang (L.), Huanglian (Franch.), Huangqin (Georgi), and nine others, which could protect against CCL4-induced liver injury by enhancing matrix metalloproteinase-2 (MMP-2) and CD147 protein expression and reducing matrix metalloproteinase inhibitor-2 expression [20].

    Non-alcoholic fatty liver disease

    NAFLD is a liver manifestation of metabolic or insulin resistance syndrome. NAFLD pathogenesis, including insulin resistance, lipid metabolic changes, mitochondrial dysfunction, oxidative stress, and other factors, are not fully clear [21]. Currently, no effective therapeutic medicine has been developed for NAFLD treatment, as it is a metabolic disease with multi-systems disorder [22]. A variety of active ingredients and formulas of TCM had been proven effective in treating NAFLD. Triterpenic acid-enriched fractions mainly extracted from Qingqianliu ()could decrease hepatic lipid accumulation and attenuate insulin resistance by upregulating the PI3K-Akt-GSK3β pathway invivoand in vitro models of NAFLD [23]. Resveratrol, a major compound in many traditional Chinese herbs such as Huzhang () [24], could reduce insulin resistance, hepatic steatosis, oxidative stress, and hepatic inflammation in rats with hyperuricemia-induced NAFLD by activating the silent information regulator 1 pathway [25].

    The adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric enzyme that plays an important role in maintaining energy metabolism homeostasis [26]. AMPK has been proven to regulate sterol regulatory element-binding protein 1 expression and acetyl-CoA carboxylases (ACC) in the liver. In vivo and in vitro studies showed that Midiexiang (Linn) could alleviate lipid metabolism in rats with orotic acid-induced NAFLD by regulating the AMPK-sterol regulatory element-binding protein 1c signaling pathway [27]. Swertiamarin is a secoiridoid glycoside mainly extracted from Zhangyacai ((Sieb. et Zucc.) Hook. Thoms. ex Clarke rude), which could regulate metabolic alterations in mice with fructose-induced NAFLD by downregulating regulatory SREBP-1, fatty acid synthase, and ACC1 expression [28]. Berberine, a protoberberine isoquinoline alkaloid mainly derived from Huanglian (Franch.), could ameliorate hyperlipidemia in rats with high-fat diet (HFD)-induced NAFLD by activating the SIRT3-AMPK-ACC pathway[29].

    In recent years, studying TCM’s mechanisms based on metabolomics, gut microbiota, and bioinformatics analyses aroused widespread concern because of the complex components of TCM. Based on metabolomics, quercetin could protect HFD-induced NAFLD in rats by regulating fatty acid-related metabolites [30]. MDG-1, a β-D-fructan polysaccharide mainly extracted from Maidong (), could modulate the gut-liver axis to regulate lipid metabolism in mice with HFD-induced NAFLD via increasing short-chain fatty acid-producing beneficial bacteria and activating AMPK expression [31]. Ilexhainanoside D and Ilexsaponin A1, the triterpenoid saponins mainly extracted from Dongqing (Merr.), could protect HFD-induced NAFLD in mice by reducing inflammation, regulating gut microbiota, and improving the intestinal barrier function [32]. Classical prescription Shen-Ling-Bai-Zhu powder is a famous formula derived fromthe ancient book of Chinese medicine(1078–1085 C.E.), mainly consists of Renshen (C. A. Mey.), Fuling (), Baizhu (Koidz.), Shanyao (Thunb), and Sharen (Lour.). Bioinformatics analysis showed that Shen-Ling-Bai-Zhu powder could protect HFD-induced NAFLD in rats by regulating hepatic microRNA expression profiles, mainly including miR-155-5p, miR-146b-5p, miR-132-3p, and miR-34a-5p [33]. In addition, Pan et al. proved that Shen-Ling-Bai-Zhu powder could also regulate hepatic lipid metabolism in HFD-fed rats by regulating glycerophospholipid and glycerolipid metabolism [34].

    Liver fibrosis

    Liver fibrosis is characterized by extracellular matrix (ECM) deposit accumulation with significant collagen fiber buildup, which is largely produced by activated hepatic stellate cells (HSCs)[35]. Several studies proved that HSC activation has been considered as the most important fibrosis-promoting factor [36]. In addition, transforming growth factor-beta1 (TGF-β1) secreted by activated HSCs is the most effective fibroblast, which induces ECM accumulation and collagen production [37]. Therefore, inhibiting HSCs activation, promoting HSC apoptosis, or regulating the TGF-β-related signaling pathways are the major mechanisms for liver fibrosis treatment. Jinyinhua (Flos)could inhibit HSC activation in mice with CCL4-induced liver fibrosis by activating the Nrf2 pathway [38]. Moreover, 4-hydroxy-2 (3H) -benzoxazolone, isolated from Laoshule (), could improve the condition of CCL4-induced liver fibrosis in rats by inhibiting the TGF-β1-Smad signaling pathway to inhibit HSC activation [39].Wenyujin ()could inhibit the activation and proliferation of HSCs in rats with pig-serum-induced hepatic fibrosis and reduce ECM accumulation by regulating the TGF-β-Smad signaling pathway and upregulating the MMP-2-matrix metalloproteinase inhibitor-1 ratio [40]. Salvianolic acid B, an effective water-soluble component of Danshen (.), could inhibit the activation of HSCs isolated from human liver specimens by downregulating the myocyte enhancer factor-2 signaling pathway [41]. Corilagin is a polyphenol mainly extracted from Zhuzicao (L.) [42], which could prevent liver fibrosis by blocking the miR-21-regulated TGF-β1-Smad signaling pathway in vivo and in vitro[43].

    In addition, transcriptomic analysis showed that schisandrin B, one of the bioactive components mainly extracted from Wuweizi (), could alleviate CCL4-induced liver fibrosis by regulating oxidation-reduction, endoplasmic reticulum stress, and apoptosis-related biological processes [44]. Based on metabolomics, bear bile powder could attenuate dimethylnitrosamine-induced liver fibrosis in rats by promoting PPARα and PPARγ expressions in the liver [45]. Network pharmacology analysis showed that the empirical formula Danshiliuhao granule, composed of Jinqiancao (), Huzhang (), Dahuang (), Zhizi (), Zhiqiao (), Muxiang (), Yanhusuo (), and Mangxiao (), could inhibit liver fibrosis by regulating multiple targets and multiple pathways, such as the PI3K-Akt-FoxO and Ras signaling pathways [46].

    Hepatocellular carcinoma

    Liver cancer is the second leading cause of cancer-related death. About 780,000 people worldwide die of liver cancer annually [47]. HCC accounts for approximately 90% of primary liver cancer[48]. However, most of the patients with HCC were diagnosed at the middle and late stage, which could not reach the standard of surgical operation. Furthermore, major cancer therapies, such as radiotherapy, chemotherapy, targeted therapeutics, and radiofrequency ablation, do not work well on HCC due to the hepatotoxicity and unresponsiveness to radio-chemotherapy [47, 49]. In addition, the first-line medicines for patients with HCC could cause adverse effects, including gastrointestinal reaction, anaphylaxis, myelosuppression, kidney damage, and neurovirulence [50].

    TCM has been proven to play an important role in cancer recurrence and metastasis prevention, toxicity reduction, and the prolonged survival of patients with cancer [49]. Several TCM active ingredients have been proven to have therapeutic effects on HCC by inhibiting cell proliferation and migration, and inducing cancer cell apoptosis.The ethanol extract of Nüzhenzi (.), which is rich in total phenylpropanoid glycosides and secoiridoids, could inhibit HCC cell invasion, migration, and tumor growth by regulating the expression of factors related to apoptosis and cell cycle arrestin vivo and in vitro[50]. Theethanol extracts of Mutong ((Thunb.) koidz seed), mainly including Akebia saponin D, Akebia saponin E, and α-hederin, could inhibit human HCC cell adhesion, migration, and invasion [51]. Aloperine, a quinolizidine alkaloid from Kudouzi (L.), could induce human HCC cell apoptosis and G2/M cell cycle arrest by inhibiting the PI3K-Akt signaling pathway [52]. Psoralen is the main active component of Buguzhi (), which could induce cell cycle arrest in the G1 phase and apoptosis, inhibit malignant proliferation of human HCC cells by triggering endoplasmic reticulum stress [53].In vitro and in vivo studies showed that dioscin, a natural steroidal saponin mainly extracted from Shuyu () [54], could inhibit proliferation and migration and induce apoptosis in human HCC cells by adjusting the TP53-inducible glycolysis and apoptosis regulator-mediated signaling pathway [55].

    In addition, the structural abnormalities of tumor vessels may reduce anticancer treatment efficacy. Normalizing the disordered tumor vasculature is a novel method for anticancer therapeutics. Huangqi () and Wenyujin () could promote vascular normalization in tumor-derived endothelial cells of human HCC by regulating CD34 and hypoxia-inducible factor-1α expressions [56]. Moreover, combination therapy with astragali polysaccharide and curcumin, the primary active constituents of Huangqi()andWenyujin() respectively, could inhibit tumor growth in orthotopic nude mice with HCC via improving the tumor vascular morphological structure and inducing tumor vascular normalization [57]. Emodin, aloe-emodin, and rhein are the main components of Dahuang (), which could inhibit the proliferation, migration, and angiogenesis and induce apoptosis of liver cancer cells by inhibiting signal transducer and activator of transcription 3 expression and phosphorylation [58].

    MiRNAs are generally considered to manage gene expression at the post-transcriptional level and are considered to be important physiologic disease progression regulators. The latest research showed that miRNAs play an important role in liver cancer occurrence and development, and they directly affect cell growth and metastasis by targeting specific protein-coding genes [59]. Luteolin, a natural flavonoid mainly extracted from Shanyao (Thunb.), could inhibit liver cancer cell proliferation by upregulating miR-6809-5p expression and downregulating flotillin 1expression [60]. Hydroxygenkwanin is a natural flavonoid mainly extracted from Yuanhua (), which could inhibit liver cancer cell proliferation and migration by inducing the expression of miR-320a, which, in turn, inhibits the expression of the forkhead box protein M1 transcription factor [48]. Geniposide is mainly extracted from Zhizi (Ellis), which could inhibit hepatoma cell proliferation and migration via inhibiting the Wnt-β-catenin and AKT cascades to target the downregulation of microRNA-224 [59].

    In addition, Saikosaponin D, an active ingredient mainly extracted from Chaihu (), could inhibit the growth and enhance the radio sensitivity of hepatoma cells by inducing autophagy [61]. Atractylon is a sesquiterpenoid mainly extracted from Cangzhu ((Thunb.) DC.) and Beicangzhu ((DC.) Koidz.), which could inhibit liver cancer cell migration and invasion by inhibiting epithelial-to-mesenchymal transition and downregulating MMP-2 and MMP-9 expressions to reduce the mitochondrial membrane potential (ΔΨm) and induce cancer cell apoptosis [62]. Chinese patent drug Shaoyao Ruangan formula (SFDA approval number of China: Z20100018) contains 19 Chinese herbal medicines, including Baihuasheshecao (Willd.), Huangqin (Georgi.), Qingyangshen (.), Wenyujin (Y. H. Chen et C. Ling.), Sanleng (Buch. -Ham.), and 14 more components,which could effectively inhibit tumor progression in mice with primary liver cancer by regulating intestinal flora homeostasis[63].

    Other liver diseases

    Hepatic encephalopathy (HE) is a neuropsychiatric disease caused by serious liver damage or failure. According to the research, 30–45% of patients with cirrhosis will develop into HE. Elevated blood ammonia levels and an abnormal electroencephalograph result are the common manifestations of HE. Hyperammonemia could impair brain metabolism, astrocyte volume regulation, and mitochondrial function, and may develop neuropsychological symptoms. Lycium barbarum polysaccharides, the major active component of Gouqizi (), could improve liver/brain injury and motor dysfunction in mice with HE by regulating the liver and brain MAPK pathways, TNF-α, interleukin-6, and ammonia [64]. Ba-Bao pill could alleviate hepatic encephalopathy in rats by reducing blood and brain ammonia levels and regulating the TLR4-MyD88-NF-κB pathway to induce anti-inflammatory effects [65].

    Acute liver failure (ALF) is a rare but life-threatening syndrome, which presents a rapid deterioration of liver function and potential multiorgan failure [66]. In vivo and in vitrostudies showed that the empirical formula Jie-Du-Hua-Yu formula, which consists of six herbs, including Chishao (), Yinchenhao (), Dahuang (), Yujin (), Baihuasheshecao (), and Shichangpu (), could treat lipopolysaccharide/D-galactosamine-induced ALF in rats by inhibiting the NF-κB-mediated inflammatory pathway [66]. Acute-on-chronic liver failure (ACLF) is a type of ALF, which is characterized by early chronic liver disease or cirrhosis combined with organ failure, and is associated with high short-term mortality [67][68]. The empirical formula Jieduan-Niwan formula contains ten Chinese herbs, including Yexiazhu (Linn.), Honghuayanhuangqi (Maxim.), Gualou (Maxim),Jinqiancao(Hance), and Hujisheng (Heyne), which could protect the liver and attenuate hepatocyte apoptosis in rats with ACLF by inhibiting the E2F1-mediated intrinsic apoptosis pathway [69]. The modified classic ancient formula Sini decoction consists of Wutou (), Gancao (), Shengjiang (), Wumei (), Renshen (), and other components, which could improve liver function and prolong the 12-week survival rate of patients with HBV-related ACLF [67].

    Conclusion and perspective

    Although Western medicine usually adopts symptomatic support to treat various chronic liver diseases, the current status of liver disease treatment is still not optimistic due to its complicated pathogenic factors and mechanisms [1]. TCM has accumulated a lot of experience in the liver disease treatment and achieved unique curative effects with the guiding concept of “holism” and the ideology of syndrome differentiation and treatment. However, the clinical curative effects of most TCM compounds are obvious, but there is lack of further laboratory experiments to prove its complex mechanics. Therefore, we summarized several researches on the active ingredients of traditional Chinese herbs used in liver disease treatment in 2019, which is mainly focused on their antioxidant effects to treat liver injury, lipid metabolism regulation to treat NAFLD, HSC inhibition to treat liver fibrosis, and inhibition of proliferation or promotion of apoptosis of liver cancer cells to treat HCC. In addition, TCM, especially the Chinese medicine formulas, is characterized by target-pathway-faceted integrated regulation because of its complex composition and structural types. Based on these findings, several researchers are committed to investigating more diversified ways to explore the specific mechanisms of TCM in treating various diseases. Therefore, metabolomics, transcriptomics, network pharmacology, 16S rRNA gene sequencing, and other omic analyses have been used in many studies. Metabolomics analysis could reflect the overall dynamic metabolic characteristics of biological systems and metabolic networks affected by pathologic stimulation or drug intervention [45]. Network pharmacology combines systemic biology, multi-directional pharmacology, bioinformatics, and other disciplines. Based on the “disease-gene-target-medicine” interaction network, it systematically observes the intervention and influence of medicines on the disease network, reflecting the new trend of systematic research of compound Chinese medicine in the era of big data [70]. The use of new omics analysis is in accordance with the concept of “holism” and could provide systematic views for future studies on TCM mechanisms [71].

    1. Shi MJ, Dong BS, Yang WN, et al. Preventive and therapeutic role of Tanshinone A in hepatology. Biomed Pharmacother 2019, 112: 108676.

    2. Sun D, Zhu L, Yao D, et al. Recent progress in potential anti-hepatitis B virus agents: structural and pharmacological perspectives. Eur J Med Chem 2018, 147: 205–217.

    3. Holleman F, Uijldert M, Donswijk LF, et al. Productivity of authors in the field of diabetes: bibliographic analysis of trial publications. BMJ 2015, 351: h2638.

    4. Wong GL, Seto WK, Wong VW, et al. Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B. Aliment Pharmacol Ther 2018, 47: 730–737.

    5. Yao X, Li Z, Gong X, et al. Total saponins extracted from Abrus cantoniensis Hance suppress hepatitis B virus replication in vitro and in rAAV8-1.3HBV transfected mice. J Ethnopharmacol 2020, 249: 112366.

    6. Chi H, Li Z, Hansen BE, et al. Serum level of antibodies against hepatitis B core protein is associated with clinical relapse after discontinuation of nucleos(t)ide analogue therapy. Clin Gastroenterol Hepatol 2019, 17: 182–191 e181.

    7. Xu L, Xie T, Shen T, et al. Yinchenhao decoction for chronic hepatitis B: protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2019, 98: e14648.

    8. Ji LS, Gao QT, Guo RW, et al. Immunomodulatory effects of combination therapy with Bushen formula plus entecavir for chronic hepatitis B patients. J Immunol Res 2019, 2019: 8983903.

    9. Tsai FJ, Cheng CF, Chen CJ, et al. Effects of Chinese herbal medicine therapy on survival and hepatic outcomes in patients with hepatitis C virus infection in Taiwan. Phytomedicine 2019, 57: 30–38.

    10. Odeyemi S, Dewar J. Repression of Acetaminophen-induced hepatotoxicity in HepG2 cells by polyphenolic compounds from(L.f.) R.H. Archer. Molecules 2019, 24.

    11. Jin Y, Huang ZL, Li L, et al. Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway. Acta Pharmacol Sin 2019, 40: 75–85.

    12. Kwon SH, Lee SR, Park YJ, et al. Suppression of 6-hydroxydopamine-induced oxidative stress by hyperoside via activation of Nrf2/HO-1 signaling in dopaminergic neurons. Int J Mol Sci 2019, 20.

    13. Wang Y, Dong B, Xue W, et al. Anticancer effect ofon cholangiocarcinoma in vitro and its mechanism via network pharmacology. Med Sci Monit 2020, 26: e921162.

    14. Rauf A, Imran M, Khan IA, et al. Anticancer potential of quercetin: a comprehensive review. Phytother Res 2018, 32: 2109–2130.

    15. Liu X, Wang Y, Wu D, et al. Magnolol prevents acute alcoholic liver damage by activating PI3K/Nrf2/PPARgamma and inhibiting NLRP3 signaling pathway. Front Pharmacol 2019, 10: 1459.

    16. Yu Y, Tian ZQ, Liang L, et al. Ba-Bao Dan attenuates acute ethanol-induced liver injury via Nrf2 activation and autophagy. Cell Biosci 2019, 9: 80.

    17. Liu F, Sun Z, Hu P, et al. Determining the protective effects of Yin-Chen-Hao Tang against acute liver injury induced by carbon tetrachloride using 16S rRNA gene sequencing and LC/MS-based metabolomics. J Pharm Biomed Anal 2019, 174: 567–577.

    18. Qiu P, Dong Y, Zhu T, et al. Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of gut-liver axis. Phytomedicine 2019, 52: 40–50.

    19. Chen Z, Zhao Y, Song C, et al. SanWeiGanJiang San relieves liver injury via Nrf2/Bach1. J Ethnopharmacol 2019, 251: 112445.

    20. Xu H, Yang N, Zhang Z, et al. Expression of matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and CD147 in the traditional Chinese medicine “Compound T11” for treatment of chronic liver injury. Pharmacology 2019, 103: 128–135.

    21. Deng Y, Tang K, Chen R, et al. Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signalling pathway. Exp Ther Med 2019, 17: 2091–2098.

    22. Hossain N, Kanwar P, Mohanty SR. A comprehensive updated review of pharmaceutical and nonpharmaceutical treatment for NAFLD. Gastroenterol Res Pract 2016, 2016: 7109270.

    23. Zheng X, Zhao MG, Jiang CH, et al. Triterpenic acids-enriched fraction fromattenuates insulin resistance and hepatic steatosis via PI3K/Akt/GSK3beta pathway. Phytomedicine 2020, 66: 153130.

    24. Wang YL, Horng CT, Hsieh MT, et al. Autophagy and apoptotic machinery caused byextract in cisplatinresistant human oral cancer CAR cells. Oncol Rep 2019, 41: 2549–2557.

    25. Xu K, Liu S, Zhao X, et al. Treating hyperuricemia related non-alcoholic fatty liver disease in rats with resveratrol. Biomed Pharmacother 2019, 110: 844–849.

    26. Park YJ, Lee GS, Cheon SY, et al. The anti-obesity effects of Tongbi-san in a high-fat diet-induced obese mouse model. BMC Complement Altern Med 2019, 19: 1.

    27. Wang SJ, Chen Q, Liu MY, et al. Regulation effects of rosemary (Linn.) on hepatic lipid metabolism in OA induced NAFLD rats. Food Funct 2019, 10: 7356–7365.

    28. Yang Y, Li J, Wei C, et al. Amelioration of nonalcoholic fatty liver disease by swertiamarin in fructose-fed mice. Phytomedicine 2019, 59: 152782.

    29. Zhang YP, Deng YJ, Tang KR, et al. Berberine ameliorates high-fat diet-induced non-alcoholic fatty liver disease in rats via activation of SIRT3/AMPK/ACC pathway. Curr Med Sci 2019, 39: 37–43.

    30. Xu Y, Han J, Dong J, et al. Metabolomics characterizes the effects and mechanisms of quercetin in nonalcoholic fatty liver disease development. Int J Mol Sci 2019, 20.

    31. Wang X, Shi L, Wang X, et al. MDG-1, anpolysaccharide, restrains process of non-alcoholic fatty liver disease via modulating the gut-liver axis. Int J Biol Macromol 2019, 141: 1013–1021.

    32. Zhao W, Xiao M, Yang J, et al. The combination of ilexhainanoside D and ilexsaponin A1 reduces liver inflammation and improves intestinal barrier function in mice with high-fat diet-induced non-alcoholic fatty liver disease. Phytomedicine 2019, 63: 153039.

    33. Pan M, Deng Y, Zheng C, et al. Chinese herbal medicine formula Shenling Baizhu San ameliorates high-fat diet-induced NAFLD in rats by modulating hepatic microRNA expression profiles. Evid Based Complement Alternat Med 2019, 2019: 8479680.

    34. Deng Y, Pan M, Nie H, et al. Lipidomic analysis of the protective effects of Shenling Baizhu San on non-alcoholic fatty liver disease in rats. Molecules 2019, 24.

    35. Wang A, Zhou F, Li D, et al. Gamma-mangostin alleviates liver fibrosis through sirtuin 3-superoxide-high mobility group box 1 signaling axis. Toxicol Appl Pharmacol 2019, 363: 142–153.

    36. Zhang Z, Guo M, Shen M, et al. Oroxylin A regulates the turnover of lipid droplet via downregulating adipose triglyceride lipase (ATGL) in hepatic stellate cells. Life Sci 2019, 238: 116934.

    37. Wang R, Song F, Li S, et al. Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways. Drug Des Devel Ther 2019, 13: 1889–1900.

    38. Chang ZY, Chen CC, Liu HM, et al. Positive effects of Ger-Gen-Chyn-Lian-Tang on cholestatic liver fibrosis in bile duct ligation-challenged mice. Int J Mol Sci 2019, 20.

    39. Sun X, Huang X, Zhu X, et al. HBOA ameliorates CCl4-incuded liver fibrosis through inhibiting TGF-beta1/Smads, NF-kappaB and ERK signaling pathways. Biomed Pharmacother 2019, 115: 108901.

    40. Xie H, Su D, Zhang J, et al. Raw and vinegar processedregulates hepatic fibrosis via bloking TGF-beta/Smad signaling pathways and up-regulation of MMP-2/TIMP-1 ratio. J Ethnopharmacol 2020, 246: 111768.

    41. Zhang W, Ping J, Zhou Y, et al. Salvianolic acid B inhibits activation of human primary hepatic stellate cells through downregulation of the myocyte enhancer factor 2 signaling pathway. Front Pharmacol 2019, 10: 322.

    42. Li X, Deng Y, Zheng Z, et al. Corilagin, a promising medicinal herbal agent. Biomed Pharmacother 2018, 99: 43–50.

    43. Zhou X, Xiong J, Lu S, et al. Inhibitory effect of corilagin on miR-21-regulated hepatic fibrosis signaling pathway. Am J Chin Med 2019, 47: 1541–1569.

    44. Zhang H, Chen Q, Dahan A, et al. Transcriptomic analyses reveal the molecular mechanisms of schisandrin B alleviates CCl4-induced liver fibrosis in rats by RNA-sequencing. Chem Biol Interact 2019, 309: 108675.

    45. Zheng M, Li YY, Wang GF, et al. Protective effect of cultured bear bile powder against dimethylnitrosamine-induced hepatic fibrosis in rats. Biomed Pharmacother 2019, 112: 108701.

    46. Tao Y, Tian K, Chen J, et al. Network pharmacology-based prediction of the active compounds, potential targets, and signaling pathways involved in Danshiliuhao granule for treatment of liver fibrosis. Evid Based Complement Alternat Med 2019, 2019: 2630357.

    47. Chou LF, Chen CY, Yang WH, et al. Suppression of hepatocellular carcinoma progression through FOXM1 and EMT inhibition via hydroxygenkwanin-induced miR-320a expression. Biomolecules 2019, 10.

    48. Zhang H, Li JC, Luo H, et al. Pseudolaric acid B exhibits anti-cancer activity on human hepatocellular carcinoma through inhibition of multiple carcinogenic signaling pathways. Phytomedicine 2019, 59: 152759.

    49. Zhang JH, Zheng C, Zhu XJ, et al. Ganji formulation for patients with hepatocellular carcinoma who have undergone surgery: a multicenter, randomized, double-blind, controlled trial. Evid Based Complement Alternat Med 2019, 2019: 9492034.

    50. Tian G, Chen J, Luo Y, et al. Ethanol extract ofait. leaves suppressed hepatocellular carcinoma in vitro and in vivo. Cancer Cell Int 2019, 19: 246.

    51. Lu WL, Yang T, Song QJ, et al.(Thunb.) Koidz seed extract inhibits human hepatocellular carcinoma cell migration and invasion in vitro. J Ethnopharmacol 2019, 234: 204–215.

    52. Liu JS, Huo CY, Cao HH, et al. Aloperine induces apoptosis and G2/M cell cycle arrest in hepatocellular carcinoma cells through the PI3K/Akt signaling pathway. Phytomedicine 2019, 61: 152843.

    53. Wang X, Peng P, Pan Z, et al. Psoralen inhibits malignant proliferation and induces apoptosis through triggering endoplasmic reticulum stress in human SMMC7721 hepatoma cells. Biol Res 2019, 52: 34.

    54. Chen B, Zhou S, Zhan Y, et al. Dioscin inhibits the invasion and migration of hepatocellular carcinoma HepG2 cells by reversing TGF-beta1-induced epithelial-mesenchymal transition. Molecules 2019, 24.

    55. Mao Z, Han X, Chen D, et al. Potent effects of dioscin against hepatocellular carcinoma through regulating TP53-induced glycolysis and apoptosis regulator (TIGAR)-mediated apoptosis, autophagy, and DNA damage. Br J Pharmacol 2019, 176: 919–937.

    56. Zang W, Bian H, Huang X, et al. Traditional Chinese medicine (TCM)andpromote vascular normalization in tumor-derived endothelial cells of human hepatocellular carcinoma. Anticancer Res 2019, 39: 2739–2747.

    57. Tang D, Zhang S, Shi X, et al. Combination of astragali polysaccharide and curcumin improves the morphological structure of tumor vessels and induces tumor vascular normalization to inhibit the growth of hepatocellular carcinoma. Integr Cancer Ther 2019, 18: 1534735418824408.

    58. Tan ZB, Fan HJ, Wu YT, et al. Rheum palmatum extract exerts anti-hepatocellular carcinoma effects by inhibiting signal transducer and activator of transcription 3 signaling. J Ethnopharmacol 2019, 232: 62–72.

    59. Yu X, Wang Y, Tao S, et al. Geniposide plays anti-tumor effects by down-regulation of microRNA-224 in HepG2 and Huh7 cell lines. Exp Mol Pathol 2020, 112: 104349.

    60. Yang PW, Lu ZY, Pan Q, et al. MicroRNA-6809-5p mediates luteolin-induced anticancer effects against hepatoma by targeting flotillin 1. Phytomedicine 2019, 57: 18–29.

    61. Tian YD, Lin S, Yang PT, et al. Saikosaponin-d increases the radiosensitivity of hepatoma cells by adjusting cell autophagy. J Cancer 2019, 10: 4947–4953.

    62. Cheng Y, Chen T, Yang X, et al. Atractylon induces apoptosis and suppresses metastasis in hepatic cancer cells and inhibits growth in vivo. Cancer Manag Res 2019, 11: 5883–5894.

    63. Zhen H, Qian X, Fu X, et al. Regulation of Shaoyao Ruangan mixture on intestinal flora in mice with primary liver cancer. Integr Cancer Ther 2019, 18: 1534735419843178.

    64. Sun X, Lv Y, Huang L, et al. Pro-inflammatory cytokines serve as communicating molecules between the liver and brain for hepatic encephalopathy pathogenesis andpolysaccharides protection. J Ethnopharmacol 2020, 248: 112357.

    65. Lu L, Wu C, Lu BJ, et al. Ba-Bao Dan cures hepatic encephalopathy by decreasing ammonia levels and alleviating inflammation in rats. J Ethnopharmacol 2020, 249: 112301.

    66. Qiu H, Mao D, Tang N, et al. The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure. Drug Des Devel Ther 2019, 13: 589–600.

    67. Luo JX, Zhang Y, Hu XY, et al. The effect of modified Sini decoction on survival rates of patients with hepatitis B virus related acute-on-chronic liver failure. Evid Based Complement Alternat Med 2019, 2019: 2501847.

    68. Ramzan M, Iqbal A, Murtaza HG, et al. Comparison of CLIF-C ACLF score and MELD score in predicting ICU mortality in patients with acute-on-chronic liver failure. Cureus 2020, 12: e7087.

    69. Yang W, Hao Y, Hou W, et al. Jieduan-Niwan formula reduces liver apoptosis in a rat model of acute-on-chronic liver failure by regulating the E2F1-mediated intrinsic apoptosis pathway. Evid Based Complement Alternat Med 2019, 2019: 8108503.

    70. Li S, Qian Y, Xie R, et al. Exploring the protective effect of ShengMai-Yin and Ganmaidazao decoction combination against type 2 diabetes mellitus with nonalcoholic fatty liver disease by network pharmacology and validation in KKAy mice. J Ethnopharmacol 2019, 242: 112029.

    71. Liu F, Wang M, Wang Y, et al. Metabonomics study on the hepatoprotective effect of panax notoginseng leaf saponins using UPLC/Q-TOF-MS analysis. Am J Chin Med 2019, 47: 559–575.

    :

    Yu-Hong Bian conceived of the presented idea; Min Cao and Jing Miao contributed to the manuscript preparation and modification with support from Yu-Hong Bian; Min Cao contributed to the hepatitis, liver injury, non-alcoholic fatty liver disease as well as conclusion and perspective in the manuscript; Jing Miao contributed to the abstract, liver fibrosis, hepatocellular carcinoma and other liver diseases in the manuscript; Li Wang, Hai-Zhao Liu and Huan-Tian Cui were responsible for searching and screening all of the literatures; all authors provided critical feedback and helped revise the final manuscript.

    :

    The authors declare no conflicts of interest.

    :

    This study was supported by Science and Technology Projects in Key Fields of Traditional Chinese Medicine of Tianjin Municipal Health Commission (No. 2020006); Tianjin Administration of Traditional Chinese Medicine, Integrated Chinese and Western Medicine Scientific Research Project of Tianjin Municipal Health Commission (No. 2017073).

    :

    TCM, traditional Chinese medicine; NAFLD, non-alcoholic fatty liver disease; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HCV, hepatitis C virus; Nrf2, nuclear factor 2-related factor 2; MMP-2, matrix metalloproteinase-2; AMPK, adenosine monophosphate-activated protein kinase; ACC, acetyl-CoA carboxylases; HFD, high-fat diet; ECM, extracellular matrix; HSC, hepatic stellate cell; TGF-β1, transforming growth factor-beta1; PPAR, peroxisome proliferator-activated receptor; HE, hepatic encephalopathy; ALF, acute liver failure; ACLF, acute-on-chronic liver failure.

    :

    Min Cao, Jing Miao, Li Wang, et al. The advances of traditional Chinese medicine in the treatment of liver diseases in 2019. Traditional Medicine Research 2020, 5 (4): 261–271.

    : Rui-Wang Zhao.

    :13 April 2020,

    14 May 2020,

    : 25 May 2020.

    #These authors are co-first authors on this work.

    Yu-Hong Bian. College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No.10 Poyanghu Road, Jinghai District, Tianjin 301617, China. E-mail: bianyuhong_2012@163.com.

    10.12032/TMR20200520182

    日韩 欧美 亚洲 中文字幕| 久久av网站| 99久久人妻综合| 欧美 日韩 精品 国产| 又紧又爽又黄一区二区| 黄色视频在线播放观看不卡| 又紧又爽又黄一区二区| 老汉色∧v一级毛片| 女人被躁到高潮嗷嗷叫费观| 精品人妻一区二区三区麻豆| 国产淫语在线视频| 狠狠婷婷综合久久久久久88av| 国产一区二区三区av在线| 欧美中文综合在线视频| 日韩 亚洲 欧美在线| 日韩 欧美 亚洲 中文字幕| 免费观看人在逋| 久久久精品国产亚洲av高清涩受| 欧美乱码精品一区二区三区| 国产亚洲av片在线观看秒播厂| 国产精品.久久久| 制服诱惑二区| xxxhd国产人妻xxx| 999久久久国产精品视频| 99国产精品免费福利视频| 久久精品成人免费网站| 中国国产av一级| 久久人人爽人人片av| 久久精品aⅴ一区二区三区四区| 黄频高清免费视频| 午夜激情久久久久久久| 日韩 亚洲 欧美在线| 日韩欧美一区视频在线观看| 国产黄色免费在线视频| 青青草视频在线视频观看| 日韩 亚洲 欧美在线| 日韩视频在线欧美| 男女下面插进去视频免费观看| 亚洲精品乱久久久久久| 在线十欧美十亚洲十日本专区| 极品少妇高潮喷水抽搐| 成在线人永久免费视频| 中文字幕人妻熟女乱码| 国产99久久九九免费精品| 丰满饥渴人妻一区二区三| 日韩欧美一区视频在线观看| 十八禁人妻一区二区| 国产激情久久老熟女| 99国产精品一区二区三区| 十八禁高潮呻吟视频| 国产在线免费精品| 精品国产一区二区久久| 日日夜夜操网爽| 婷婷成人精品国产| 欧美激情极品国产一区二区三区| 人人妻人人澡人人看| 啦啦啦中文免费视频观看日本| 婷婷色av中文字幕| 日韩熟女老妇一区二区性免费视频| 后天国语完整版免费观看| 丰满迷人的少妇在线观看| 少妇 在线观看| 久久国产精品男人的天堂亚洲| 99精国产麻豆久久婷婷| 日本vs欧美在线观看视频| 在线观看免费高清a一片| 人妻人人澡人人爽人人| av片东京热男人的天堂| 亚洲国产成人一精品久久久| 黄网站色视频无遮挡免费观看| 黄色毛片三级朝国网站| 伦理电影免费视频| 精品一区二区三区av网在线观看 | 肉色欧美久久久久久久蜜桃| 久久免费观看电影| 99香蕉大伊视频| 欧美一级毛片孕妇| 中国国产av一级| 欧美另类亚洲清纯唯美| 我的亚洲天堂| 国产免费视频播放在线视频| 老司机亚洲免费影院| 亚洲精品国产av蜜桃| 黑人巨大精品欧美一区二区蜜桃| 久久天堂一区二区三区四区| 欧美日韩视频精品一区| 亚洲av片天天在线观看| 丝瓜视频免费看黄片| 成在线人永久免费视频| 国产精品 欧美亚洲| 久热爱精品视频在线9| 国产精品久久久人人做人人爽| 免费看十八禁软件| 啦啦啦在线免费观看视频4| 久久久久久久大尺度免费视频| 亚洲精品美女久久久久99蜜臀| 久久精品久久久久久噜噜老黄| 91精品伊人久久大香线蕉| 嫩草影视91久久| 黑丝袜美女国产一区| 日本撒尿小便嘘嘘汇集6| 国产亚洲精品一区二区www | 黄色 视频免费看| 19禁男女啪啪无遮挡网站| 国产麻豆69| 女人爽到高潮嗷嗷叫在线视频| 丁香六月天网| 亚洲人成电影观看| 黑人欧美特级aaaaaa片| 韩国精品一区二区三区| 亚洲精品美女久久久久99蜜臀| 国产成人精品在线电影| 日本av手机在线免费观看| 夜夜夜夜夜久久久久| 精品久久蜜臀av无| 男女国产视频网站| 日韩免费高清中文字幕av| 曰老女人黄片| av线在线观看网站| 男人添女人高潮全过程视频| 女性生殖器流出的白浆| 老鸭窝网址在线观看| 国产色视频综合| 老司机午夜十八禁免费视频| 18禁裸乳无遮挡动漫免费视频| 久久人人爽av亚洲精品天堂| 一本久久精品| 免费在线观看视频国产中文字幕亚洲 | 亚洲 欧美一区二区三区| 高清欧美精品videossex| 午夜激情av网站| 精品人妻1区二区| 精品少妇黑人巨大在线播放| 欧美精品一区二区大全| 成年女人毛片免费观看观看9 | 欧美黑人精品巨大| 一个人免费在线观看的高清视频 | 国产成人免费无遮挡视频| 亚洲午夜精品一区,二区,三区| 女人被躁到高潮嗷嗷叫费观| 80岁老熟妇乱子伦牲交| 大陆偷拍与自拍| 丝袜人妻中文字幕| 亚洲免费av在线视频| 91大片在线观看| netflix在线观看网站| 一边摸一边做爽爽视频免费| tube8黄色片| 十八禁网站网址无遮挡| 最近最新中文字幕大全免费视频| 嫁个100分男人电影在线观看| 日本撒尿小便嘘嘘汇集6| 久久国产精品人妻蜜桃| 欧美人与性动交α欧美软件| 亚洲专区中文字幕在线| 亚洲精品美女久久久久99蜜臀| 成年人黄色毛片网站| 亚洲第一欧美日韩一区二区三区 | 正在播放国产对白刺激| 99热全是精品| 国产不卡av网站在线观看| 麻豆av在线久日| 十八禁人妻一区二区| 美女扒开内裤让男人捅视频| 黄色怎么调成土黄色| 中亚洲国语对白在线视频| 午夜久久久在线观看| 老司机深夜福利视频在线观看 | 这个男人来自地球电影免费观看| 国产国语露脸激情在线看| 久久久国产一区二区| 老熟妇乱子伦视频在线观看 | 亚洲黑人精品在线| 夜夜夜夜夜久久久久| 午夜91福利影院| 久久久久久久国产电影| 一二三四社区在线视频社区8| 日韩大码丰满熟妇| svipshipincom国产片| 在线 av 中文字幕| 在线观看人妻少妇| 欧美激情高清一区二区三区| 亚洲国产av影院在线观看| 丁香六月欧美| 日韩一区二区三区影片| 日韩欧美一区二区三区在线观看 | a级毛片黄视频| 涩涩av久久男人的天堂| 国产又色又爽无遮挡免| cao死你这个sao货| 自线自在国产av| 国产成人一区二区三区免费视频网站| 精品国产乱码久久久久久小说| 黄片播放在线免费| 一区二区三区激情视频| av在线老鸭窝| 99国产精品免费福利视频| 交换朋友夫妻互换小说| 大型av网站在线播放| 老司机亚洲免费影院| 国产欧美日韩一区二区三区在线| 亚洲久久久国产精品| 麻豆av在线久日| av又黄又爽大尺度在线免费看| 人人妻人人澡人人看| 亚洲七黄色美女视频| 精品国产乱码久久久久久小说| 2018国产大陆天天弄谢| 久久国产亚洲av麻豆专区| 超碰97精品在线观看| 他把我摸到了高潮在线观看 | 大陆偷拍与自拍| 国产精品亚洲av一区麻豆| 欧美人与性动交α欧美软件| 涩涩av久久男人的天堂| 最近中文字幕2019免费版| 精品一区二区三区四区五区乱码| 国产1区2区3区精品| 国产一级毛片在线| 捣出白浆h1v1| 国产色视频综合| 青青草视频在线视频观看| 久久久久久免费高清国产稀缺| kizo精华| 国产av精品麻豆| 欧美亚洲日本最大视频资源| 国产主播在线观看一区二区| 51午夜福利影视在线观看| 精品一区二区三区四区五区乱码| 国产1区2区3区精品| 韩国精品一区二区三区| 成年人免费黄色播放视频| 国产欧美日韩一区二区精品| 黄色a级毛片大全视频| 亚洲三区欧美一区| 免费少妇av软件| 成年美女黄网站色视频大全免费| 老司机午夜福利在线观看视频 | 国产区一区二久久| 精品国产国语对白av| 97在线人人人人妻| 久久久国产成人免费| 国产精品久久久久久精品电影小说| 久久久久精品人妻al黑| 久久ye,这里只有精品| 新久久久久国产一级毛片| 国产黄频视频在线观看| 精品福利观看| 欧美日韩亚洲综合一区二区三区_| 久久午夜综合久久蜜桃| 日韩精品免费视频一区二区三区| 女人精品久久久久毛片| 成年av动漫网址| 最近最新免费中文字幕在线| 超碰成人久久| 美女高潮到喷水免费观看| 久久久国产一区二区| 成年av动漫网址| 欧美日本中文国产一区发布| 国产高清视频在线播放一区 | 18禁国产床啪视频网站| 久久精品国产亚洲av香蕉五月 | 国产精品一区二区精品视频观看| 欧美av亚洲av综合av国产av| 男女之事视频高清在线观看| 美女扒开内裤让男人捅视频| 国产日韩欧美视频二区| 亚洲男人天堂网一区| 99热国产这里只有精品6| 午夜日韩欧美国产| 亚洲专区中文字幕在线| 99国产综合亚洲精品| 日韩大片免费观看网站| 欧美激情久久久久久爽电影 | 久久久久久久大尺度免费视频| 国产免费现黄频在线看| 亚洲成国产人片在线观看| 手机成人av网站| 国产精品二区激情视频| 桃花免费在线播放| 大片免费播放器 马上看| kizo精华| 正在播放国产对白刺激| 久久精品国产亚洲av香蕉五月 | 香蕉丝袜av| 日日摸夜夜添夜夜添小说| 在线永久观看黄色视频| 免费久久久久久久精品成人欧美视频| 日韩视频在线欧美| 91麻豆av在线| 巨乳人妻的诱惑在线观看| 极品人妻少妇av视频| 国产成人欧美| 欧美日韩视频精品一区| 国产无遮挡羞羞视频在线观看| av网站免费在线观看视频| 欧美日韩国产mv在线观看视频| 高清视频免费观看一区二区| 亚洲国产精品一区三区| 宅男免费午夜| 91大片在线观看| 欧美黑人精品巨大| 国产亚洲午夜精品一区二区久久| 国产xxxxx性猛交| e午夜精品久久久久久久| 久久久久久人人人人人| 亚洲色图 男人天堂 中文字幕| 欧美精品亚洲一区二区| 母亲3免费完整高清在线观看| 亚洲精品国产av成人精品| 成人免费观看视频高清| 99国产精品99久久久久| 视频区欧美日本亚洲| 午夜免费鲁丝| 精品乱码久久久久久99久播| 制服人妻中文乱码| 搡老岳熟女国产| 后天国语完整版免费观看| 一本大道久久a久久精品| 天天躁夜夜躁狠狠躁躁| 成年人午夜在线观看视频| 十八禁高潮呻吟视频| av超薄肉色丝袜交足视频| 两个人看的免费小视频| 欧美日韩黄片免| 99国产综合亚洲精品| 男女国产视频网站| 狠狠精品人妻久久久久久综合| 香蕉丝袜av| 成人18禁高潮啪啪吃奶动态图| 久久精品国产a三级三级三级| 天天操日日干夜夜撸| 人人澡人人妻人| 免费黄频网站在线观看国产| 国产黄色免费在线视频| 丝袜美足系列| 精品国产一区二区三区四区第35| 亚洲天堂av无毛| 人妻人人澡人人爽人人| 亚洲成人国产一区在线观看| 黄色片一级片一级黄色片| 丰满少妇做爰视频| 丝袜美腿诱惑在线| 两性午夜刺激爽爽歪歪视频在线观看 | 亚洲五月婷婷丁香| 欧美日韩黄片免| 青草久久国产| 12—13女人毛片做爰片一| 制服诱惑二区| 久久久久久久国产电影| 亚洲国产av新网站| 女人高潮潮喷娇喘18禁视频| 18禁裸乳无遮挡动漫免费视频| 国产日韩欧美亚洲二区| 久久久久视频综合| 久久狼人影院| 免费av中文字幕在线| 欧美黑人精品巨大| 久久ye,这里只有精品| 日韩欧美一区二区三区在线观看 | 国产成人欧美| 久久久国产成人免费| 国产精品久久久久久精品古装| 免费人妻精品一区二区三区视频| 欧美日韩黄片免| 日本av免费视频播放| 不卡一级毛片| 99热国产这里只有精品6| 午夜精品国产一区二区电影| 热99re8久久精品国产| 国产欧美日韩一区二区三区在线| 日韩制服骚丝袜av| 男女午夜视频在线观看| 亚洲成国产人片在线观看| 无遮挡黄片免费观看| 久久久久久亚洲精品国产蜜桃av| 久久国产精品男人的天堂亚洲| 国产男人的电影天堂91| 精品一品国产午夜福利视频| 成人影院久久| 国产在线视频一区二区| av国产精品久久久久影院| 一二三四社区在线视频社区8| 亚洲精品久久午夜乱码| 成人免费观看视频高清| 国产亚洲精品一区二区www | 国产免费现黄频在线看| av电影中文网址| 久久人妻熟女aⅴ| 老司机影院成人| 51午夜福利影视在线观看| 又黄又粗又硬又大视频| 亚洲欧美精品自产自拍| 亚洲专区国产一区二区| 亚洲五月婷婷丁香| 女人被躁到高潮嗷嗷叫费观| 国产麻豆69| 天天躁夜夜躁狠狠躁躁| 色婷婷av一区二区三区视频| 国产一区有黄有色的免费视频| 亚洲综合色网址| 精品人妻在线不人妻| 成人国语在线视频| 亚洲精品中文字幕在线视频| 飞空精品影院首页| 国产免费av片在线观看野外av| 国产极品粉嫩免费观看在线| 国产精品免费视频内射| 欧美亚洲 丝袜 人妻 在线| 欧美成人午夜精品| 欧美日韩视频精品一区| 乱人伦中国视频| 免费不卡黄色视频| 精品视频人人做人人爽| 亚洲国产精品一区三区| 五月开心婷婷网| 99久久综合免费| 中文字幕另类日韩欧美亚洲嫩草| 97人妻天天添夜夜摸| 免费看十八禁软件| 12—13女人毛片做爰片一| 亚洲欧美成人综合另类久久久| 新久久久久国产一级毛片| 精品欧美一区二区三区在线| 国产又色又爽无遮挡免| 窝窝影院91人妻| 亚洲av电影在线进入| av电影中文网址| 大型av网站在线播放| 精品少妇一区二区三区视频日本电影| 久9热在线精品视频| 99久久人妻综合| 精品久久蜜臀av无| kizo精华| 国产1区2区3区精品| 久久中文字幕一级| 国产精品99久久99久久久不卡| 最新的欧美精品一区二区| 国产精品久久久久久精品古装| 99久久国产精品久久久| 国产成人系列免费观看| svipshipincom国产片| 美女高潮喷水抽搐中文字幕| 少妇猛男粗大的猛烈进出视频| 欧美日韩亚洲综合一区二区三区_| 岛国在线观看网站| 91国产中文字幕| 好男人电影高清在线观看| 99热网站在线观看| 日韩欧美一区视频在线观看| 亚洲精品久久午夜乱码| 叶爱在线成人免费视频播放| 亚洲欧美精品综合一区二区三区| 午夜精品久久久久久毛片777| 丝瓜视频免费看黄片| 老司机午夜福利在线观看视频 | 久久这里只有精品19| 亚洲av成人不卡在线观看播放网 | 亚洲男人天堂网一区| 黄色a级毛片大全视频| 午夜福利免费观看在线| 在线 av 中文字幕| 国产色视频综合| 韩国精品一区二区三区| 美女扒开内裤让男人捅视频| 亚洲久久久国产精品| 王馨瑶露胸无遮挡在线观看| 美女大奶头黄色视频| 亚洲精品国产区一区二| 国产97色在线日韩免费| 国产又色又爽无遮挡免| 国产成人a∨麻豆精品| 国产免费福利视频在线观看| 动漫黄色视频在线观看| 操美女的视频在线观看| 考比视频在线观看| 免费一级毛片在线播放高清视频 | 美女扒开内裤让男人捅视频| 亚洲精品美女久久久久99蜜臀| 亚洲欧美一区二区三区久久| 男女边摸边吃奶| 久久久久久人人人人人| 欧美一级毛片孕妇| 一本一本久久a久久精品综合妖精| 精品高清国产在线一区| 亚洲黑人精品在线| 一边摸一边做爽爽视频免费| 麻豆av在线久日| 久久人人爽人人片av| 视频在线观看一区二区三区| 汤姆久久久久久久影院中文字幕| 无限看片的www在线观看| 在线天堂中文资源库| 国产精品一区二区免费欧美 | 久久精品久久久久久噜噜老黄| 欧美日韩亚洲高清精品| 欧美日韩视频精品一区| 亚洲精品在线美女| 在线观看免费日韩欧美大片| 国产日韩欧美视频二区| 亚洲激情五月婷婷啪啪| 欧美激情久久久久久爽电影 | 久久精品aⅴ一区二区三区四区| 2018国产大陆天天弄谢| 亚洲国产毛片av蜜桃av| 两人在一起打扑克的视频| 国产亚洲av片在线观看秒播厂| 亚洲免费av在线视频| 日韩欧美国产一区二区入口| 亚洲一卡2卡3卡4卡5卡精品中文| 国产高清视频在线播放一区 | 国产欧美日韩一区二区三区在线| 精品熟女少妇八av免费久了| 少妇粗大呻吟视频| 大码成人一级视频| 国产欧美日韩精品亚洲av| 亚洲专区字幕在线| 中文欧美无线码| 无遮挡黄片免费观看| 久久国产精品人妻蜜桃| 欧美激情高清一区二区三区| 在线观看www视频免费| 女人精品久久久久毛片| 免费在线观看完整版高清| 人妻人人澡人人爽人人| 亚洲五月婷婷丁香| 少妇精品久久久久久久| 久久综合国产亚洲精品| 欧美xxⅹ黑人| 欧美日韩黄片免| 精品久久蜜臀av无| 欧美日本中文国产一区发布| 美女国产高潮福利片在线看| 欧美人与性动交α欧美精品济南到| 国产日韩欧美在线精品| 精品国内亚洲2022精品成人 | 两个人免费观看高清视频| 99国产精品99久久久久| 色精品久久人妻99蜜桃| 好男人电影高清在线观看| svipshipincom国产片| 人人妻人人澡人人爽人人夜夜| a 毛片基地| 精品国产乱码久久久久久小说| 一区福利在线观看| 啦啦啦视频在线资源免费观看| 久久99一区二区三区| 久久久久久久大尺度免费视频| 2018国产大陆天天弄谢| 欧美日韩中文字幕国产精品一区二区三区 | 黄色毛片三级朝国网站| av超薄肉色丝袜交足视频| 老熟女久久久| 国产人伦9x9x在线观看| 精品国产乱码久久久久久男人| 另类精品久久| 大片电影免费在线观看免费| 在线天堂中文资源库| 欧美日韩精品网址| 久久久精品国产亚洲av高清涩受| 蜜桃在线观看..| 亚洲欧美清纯卡通| 久9热在线精品视频| 在线观看免费视频网站a站| 久久99热这里只频精品6学生| cao死你这个sao货| 老熟女久久久| 精品第一国产精品| 亚洲精品中文字幕一二三四区 | 国产成人精品在线电影| 日韩一区二区三区影片| 99香蕉大伊视频| 91成人精品电影| 中文精品一卡2卡3卡4更新| 精品乱码久久久久久99久播| 中文字幕高清在线视频| 精品国产乱码久久久久久男人| 亚洲精品一卡2卡三卡4卡5卡 | 一本久久精品| 亚洲精品自拍成人| 久久久久久人人人人人| 国产成人欧美在线观看 | 亚洲三区欧美一区| 日本wwww免费看| 亚洲精品久久成人aⅴ小说| 亚洲国产精品一区三区| 性高湖久久久久久久久免费观看| 国产精品熟女久久久久浪| 久久精品成人免费网站| 久久久久久久国产电影| 久久久久国产一级毛片高清牌| 他把我摸到了高潮在线观看 | 啦啦啦在线免费观看视频4| 成年美女黄网站色视频大全免费| 在线亚洲精品国产二区图片欧美| 国产精品欧美亚洲77777| 久久女婷五月综合色啪小说| 激情视频va一区二区三区| av网站在线播放免费| 久久久国产精品麻豆| 建设人人有责人人尽责人人享有的| 婷婷丁香在线五月| 国产成人精品在线电影| 久久久久久免费高清国产稀缺| 免费久久久久久久精品成人欧美视频| 天天添夜夜摸| 动漫黄色视频在线观看| 日本猛色少妇xxxxx猛交久久| 99精国产麻豆久久婷婷| 女人被躁到高潮嗷嗷叫费观| 伦理电影免费视频| 51午夜福利影视在线观看| 欧美+亚洲+日韩+国产| 久久人人爽av亚洲精品天堂| 久久久久久久久久久久大奶|