Advances in traditional Chinese medicine for liver disease therapy in 2020

Liver diseases are gradually becoming a serious threat to human health worldwide.Although a number of medications have been introduced for the prophylaxis,diagnosis,and treatment of liver diseases,several limitations and challenges remain.Traditional Chinese medicine is frequently used to treat liver diseases and well known to protect hepatocytes and inhibit inflammation,oxidative stress,and fibrosis.However,given the complex composition of traditional Chinese medicine,clarifying the mechanisms behind its curative and protective effects is difficult.In this review,research progress on traditional Chinese medicine for the treatment of liver diseases in 2020 is summarized on the basis of the literature available in the PubMed database.Herbal extracts derived from traditional Chinese medicine,including flavonoids,polysaccharides,saponins,and alkaloids,and Chinese medicinal formulas,such as the classic decoctions Chaihu Shugan powder,Linggui Zhugan decoction,and Huanglian Jiedu decoction,have shown promising therapeutic efficacy in liver disease treatment.We summarized the findings of several studies on the active ingredients of traditional Chinese herbs used for liver disease treatment in 2020,focusing mainly on their ability to confer antiviral effects to treat hepatitis,regulate antioxidant levels and apoptosis to treat liver injury,inhibit inflammation and improve dysfunctions in amino acids and energy metabolism to treat alcoholic liver disease,reduce hepatic lipid deposition to treat nonalcoholic fatty liver disease,promote activated hepatic stellate cells to treat liver fibrosis,inhibit the proliferation or promote the apoptosis of liver cancer cells to treat hepatocellular carcinoma,and improve bile acid metabolism to treat cholestasis.

Inhibition of Pathological Angiogenesis of Chinese Medicine against Liver Fibrosis

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells（LSECs） and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fibrosis through inhibiting angiogenesis.

Advances in mesenchymal stem cells combined with traditional Chinese medicine therapy for liver fibrosis

Liver fibrosis is a primary cause of liver cirrhosis, and even hepatocarcinoma. Recently, the usage of mesenchyrnal stem cells （MSCs） has been investigated to improve liver fibrosis. It has been reported that the differentiation, proliferation and migration of MSCs can be regulated by traditional Chinese medicine treatment; however, the mechanisms are still unclear. In this article, the authors review the characteristics of MSCs such as multidirectional differentiation and homing, and its application in animal experiments and clinical trials. The authors also list areas that need further investigation, and look at the future prospects of clinical application of MSCs.

Angiogenesis and Hepatic Fibrosis： Western and Chinese Medicine Therapies on the Road

Hepatic fibrosis is a common feature of almost all chronic liver diseases. Formation of new vessels （angiogenesis） is a process strictly related to the progressive fibrogenesis which leads to cirrhosis and liver cancer. This review mainly concerns the relationship between angiogenesis and hepatic fibrosis, by considering the mechanism of angiogenesis, cells in angiogenesis, anti-angiogenic and Chinese medicine therapies.

Thrombospondin-1 expression correlates with angiogenesis in experimental cirrhosis

AIM:To investigate the significance of Thrombospondin-1 (TSP-1) expression and its relationship with angiogenesis during experimental fibrosis. METHODS:Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN). The serial sections from liver tissues were stained with anti-CD34 and anti-TSP-1 antibodies before being quantitated by light microscopy. RESULTS:Our results showed that of TSP-1 expression gradually increases according to the severity of fibrosis (GroupⅠvs group Ⅱ, Group Ⅲ and Group Ⅳ;Group Ⅱ vs group Ⅲ and group Ⅳ;group Ⅲ vs group Ⅳ, P < 0.05). Moreover, TSP-1 expression was found to be correlated with angiogenesis (P < 0.05). CONCLUSION:The correlative evidence of the link between TSP-1 and fibrosis or angiogenesis provided by this study suggests that besides its role as a strong promoter of transforming growth factor-β1 (TGF-β1), TSP-1 might have an additional role in liver fibrogenesis by stimulating angiogenesis and this protein could be a potential target to prevent fibrogenesis in chronic inflammatory diseases of the liver.

Experimental and Clinical Study on Inhibition and Reversion of Liver Fibrosis with Integrated Chinese and Western Medicine

Objective: To explore the possibility of reverting HBV-related hepatic fibrosis and cirrhosiswith traditional Chinese medicine (TCM). Methods: A herbal recipe (861 ), comprising of 10 herbs includingSalvia miltiorrhiza, Astragalus membranaceus and SPatholobus saberectus were used as the antifibrotic agents. Three controlled clinical trials of treating HBV-related fibrosis and early cirrhosis were carried out. A total of 107 patients were assessed clinically and pathologically with double liver biopsies before and after treatmentby means of modified Scheuer and Chevallier scoring system. Rat model of hepatic fibrosis induced by CCI. andhuman albumin immune injury, culture of separated hepatic stellate cells (HSC) were established. Total collagen content of the liver was determined by detection of hydroxyproline, amount of type Ⅰ, Ⅲ Ⅳ collagens byhistoimmunochemistry, quantitative measurement of mRNA for collagen Ⅰ, Ⅲ, Ⅳ, transforming growth factor-3 (TGF-3), matrix metalloproteinase (MMPI ), MMP2, tissue inhibitor of metalloproteinase (TIMP) inliver tissue by dot blot hybridization. Serum and liver tissue collagenase activity was detected by method of Rajabi M and Emonard H. Histopathological study of liver specimen was done with H. E., Masson and sirius redstain as well as histoimmunochemistry. Results: (1 ) In HBV-related patients, after six months treatment with861, the reversion rate was as high as 78% in S2, 82 % in S3 (precirrhotic stage) and 75 % in S4 (cirrhosis).These results corresPOnd well with that obtained in animal experiment. (2) Total and type i, m, V collagencontent in animal model liver were significantly reduced in amount after 861 treatment, whereas quantitation ofmRNA for collagen Ⅰ, Ⅲ, Ⅳ and TGF-β were also markedly suppressed either in liver tissue or cultured HSC,suggesting the suppression by 861 on fibrogenesis. At the same time, serum and liver tissue collagenase activity(latent and active) were enhanced significantly by administration of 861, while mRNA for MMPI (interstitialcollagenase) in cultured HSC and collagenase activity in the supernatant of the HSC culture were both increased,and meantime, mRNA for TIMPI was significantly suppressed in quantity, indicating the enhancement of excessive extracellular matrix (ECM) degradation after 861 treatment. Conclusions: (l ) Contrary to the conventional concept, the liver fibrosis and early cirrhosis due to HBV infection in man could be definitely reversed byTCM treatment of 861. This was also verified in CC14 and immune injury models. (2) The mechanism leadingto the reversal of fibrosis was due to suppression of fibrogenesis, and the concurrent enhancement of ECM degradation. In the latter, suppression of TIMP also plays an imPOrtant role. (3) Both initiation by imflammationand perpetuation of the activation of HSC were suppressed by the 861.

Bone Marrow Angiogenesis in Patients Presenting with Differential Chinese Medicine Syndrome:Correlation with the Clinico-pathological Features of Aplastic Anemia

Objective： To explore differences in bone marrow angiogenesis seen in aplastic anemia （AA） patients presenting with differential Chinese medicine （CM） syndrome, and to correlate these differences with clinical pathology. Methods： Thirty-five patients were enrolled, including 18 with ＂yang deficiency syndrome＂ and 17 with ＂yin deficiency syndrome.＂ Bone marrow biopsies and serum were collected. Microvessel density （MVD） and positive expression of vascular endothelial-derived growth factor （VEGF） were detected by immunohistochemisty. Hypoxia inducible factor -α （HIF-α ）, and VEGF expression were assayed by enzyme-linked immunoabsorbent assay （ELISA）, serum lactate dehydrogenase （LDH） was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin （IL）-2, IL-4, IL-6, IL-10, interferon （IFN）-＇y and tumor necrosis factor （TNF）-α. Results： Counts for leukocytes, absolute neutrophils and platelets in ＂yin deficiency syndrome＂ were lower than those found in ＂yang deficiency syndrome＂ （P〈0.05）. MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in hA, especially in ＂yin deficiency syndrome＂ （P〈0.01 or P〈0.05）. ＂Yin deficiency syndrome＂ displayed decreased VEGF and LDH expression, and enhanced expression of HIF-α as compared to ＂yang deficiency syndrome＂ （P〈0.05）. Levels of IL-4 and IL-6 were higher in AA （P〈0.01）, but IL-10 was decreased （P〈0.05）. High TNF-c~ expression was seen in ＂yang deficiency syndrome＂ and IFN- γ expression was decreased in ＂yin deficiency syndrome＂ as compared with normals （P〈0.01 and P〈0.05, respectively）. Conclusion： AA patients have lower MVD than normals, especially in ＂yin deficiency syndrome.＂ MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN- γ were negatively associated while IL-6 and TNF- α were positively associated with MVD.

Study on the Effect of Chinese Herbal Medicine in Regulating Peritoneal Lymphatic Stomata and Enhancing Drainage of Ascites in Mice with Liver Fibrosis

Objective: To observe the regulating effect of Chinese herbal medicine on peritoneal lymphatic stomata and its significance in treating ascites in liver fibrosis model mice. Methods: Two Chinese herbal compound prescriptions were used separately to treat the carbon tetrachloride induced mouse model of liver fibrosis, the histo-pathologic changes in mice were observed by using scanning electron microscope and processed by computer image processing. The changes of urinary volume and sodium ion concentration were measured, too.Results: In the treated group, the histo-pathologic changes were significantly less than those in the control group, the peritoneal lymphatic stomata enlarged with increased number of opening and higher density in distribution and the urinary volume and sodium ion excretion increased after treatment. Conclusion: Chinese herbal medicine has marked effect in alleviating liver fibrosis, regulating peritoneal lymphatic stomata, improving the drainage of ascites from peritoneal cavity, causing increase of urinary volume and sodium ion excretion to reduce water and sodium retention, and thus have favorable therapeutic effect in treating ascites.

细胞焦亡在肝纤维化中的作用及中医药调控研究进展

肝纤维化(HF)是肝损伤后的重要病理修复过程,阻断HF发展是阻止其向肝硬化、肝癌或肝衰竭转变的重要环节,目前尚缺乏理想的治疗HF的特效药物。细胞焦亡是一种新型的程序性细胞死亡方式,以细胞膜上孔隙形成和促白细胞介素(IL)-18、IL-1β生成释放为表现。在肝脏受到持续损伤时肝星状细胞、肝巨噬细胞和肝细胞均会发生细胞焦亡,进而持续激活炎症反应,导致肝脏结构被破坏,最终引起HF。中医药在抗HF过程中具有多靶点、多途径等优势,中药及其活性成分、中药药对及中药复方均可通过抑制细胞焦亡而发挥抗HF的作用,以中医药调节细胞焦亡作为切入点可能是未来治疗HF的新方向。该文总结了细胞焦亡的分子机制、肝脏各个类型细胞发生焦亡与HF的关系,以及中药及其活性成分、中药药对及中药复方通过抑制肝脏细胞发生焦亡进而阻止HF进程的相关研究,以期为进一步的临床研究及试验提供参考依据。

气血通化方联合恩替卡韦对慢性乙型肝炎患者TBil、LSM及临床症状的影响

目的:探讨并验证在学术传承观点指导下的气血通化方在慢性乙型肝炎患者治疗中的应用效果。方法:将2021年1月至2023年6月在南昌市第九医院就诊50例慢性乙型肝炎患者分为对照组和观察组,每组25例,对照组患者采用恩替卡韦治疗,观察组联合中药气血通化方治疗,治疗24周后观察治疗前后TBil、LSM的变化及临床疗效。结果:治疗后观察组患者总胆红素(TBil)、肝脏硬度值(LSM)低于对照组,差异具统计学意义(P<0.05);治疗后观察组患者中医总症状积分低于对照组,差异具统计学意义(P<0.05);观察组不良反应总发生率4.35%(3/69),对照组7.25%(5/69),差异无统计学意义(P>0.05)。结论:在“气血通化”学术观点指导下,恩替卡韦联合气血通化方治疗更有助于肝纤维化、总胆红素及症状改善,提高临床疗效。

调控肝星状细胞糖酵解抗肝纤维化的机制及中医药防治研究进展

肝星状细胞(Hepatic stellate cell,HSC)活化是肝纤维化发生发展过程中的关键环节。活化HSC的代谢重编程已成为当前研究的热点,尤其糖酵解的改变是调控HSC活化的重要因素。该文基于HSC活化过程中的代谢重编程,阐述了通过糖酵解调控HSC活化及肝纤维化的机制,并对中药及其活性成分调节HSC糖酵解防治肝纤维化的研究进展进行了综述。肝纤维化是涉及多因素、多通路的复杂病理过程,调节活化HSC的糖酵解为抗肝纤维化药物的研发提供了一种新思路。

疏肝理气活血汤联合常规西药治疗慢性萎缩性胃炎临床研究

目的:观察疏肝理气活血汤联合常规西药治疗肝胃不和型慢性萎缩性胃炎(CAG)的临床疗效。方法:选择肝胃不和型CAG患者80例,按照随机数字表法分为观察组和对照组各40例。对照组给予枸橼酸莫沙必利片和瑞巴派特片治疗,观察组在对照组基础上加用疏肝理气活血汤治疗。评价2组临床疗效,比较2组治疗前后中医证候积分及病理检查评分,统计不良反应发生率。结果:观察组总有效率为85.00%,高于对照组70.00%(P<0.05)。治疗后,2组中医证候积分较治疗前下降(P<0.05),且观察组中医证候积分低于对照组(P<0.05)。治疗后,2组胃黏膜萎缩、肠上皮化生、异型增生评分较治疗前下降(P<0.05);且观察组胃黏膜萎缩、肠上皮化生、异型增生评分低于对照组(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:疏肝理气活血汤联合常规西药治疗CAG可改善患者的临床症状,对于缓解或逆转胃黏膜萎缩、肠上皮化生和异型增生具有一定的治疗效果,且不良反应较少。

中西医结合治疗肝郁脾虚型乙型肝炎肝纤维化的研究进展

乙型肝炎病毒(HBV)是引起肝纤维化(HF)及肝硬化的最常见原因之一。虽然针对HBV引起的HF行病因治疗可以取得较好的病毒学应答,但HF仍然存在并不断进展,故抗HF的用药仍值得商榷。近年来,中医在其独有的辨证论治基础上治疗HF已获得一定的临床效果,中西医结合治疗慢性乙型肝炎HF已成为一大热点。研究表明肝郁脾虚型慢性乙型肝炎HF出现相对较早,主要见于HF早期(S1)以及肝组织病理分级G1、G2,是中医控制并逆转HF的重要节点。本文综述近十年中药复方联合恩替卡韦、阿德福韦酯、干扰素、替诺福韦抗病毒药物治疗肝郁脾虚型慢性乙型肝炎HF的研究进展,为临床用药与新药研发提供更多参考。

中医药通过调节糖代谢治疗原发性肝癌的研究进展

原发性肝癌(PLC)是最常见的消化道恶性肿瘤之一,发病早期无明显临床症状,发现时大多数已为晚期,且治疗手段比较单一,疗效一般,给人民生命、财产安全带来了巨大威胁。近年研究发现糖代谢与PLC的形成、进展密切相关,在多种病因所致肝癌临床病例和动物模型中均发现有糖代谢的参与,为PLC的治疗提供了新思路。中医药对PLC整体疗效十分确切,特别是在延长患者生存期、提升患者生命质量以及降低肿瘤复发风险等方面效果显著。

外泌体在中医药防治肝纤维化中的应用研究

外泌体是肝纤维化潜在的病理介质、标志物和治疗靶点,具有广泛性、组织源性、靶向性和生物功能性等特点。目前已发现血清外泌体中长链非编码RNA(long non-coding RNA,LncRNA)和microRNA(miRNA)可作为肝纤维化早期诊断标志物;外泌体内相关遗传物质的改变可为肝纤维化微观辨证的证候研究提供更加客观的指标参考;外泌体或可能是中药有效成分的潜在作用靶点,能更全面地体现中药治疗肝纤维化多途径、多靶点的特性;外泌体又可作为中药载体进行靶向运输,可显著提高中药有效成分的抗肝纤维化疗效。外泌体的发现不仅可为今后中医药在肝纤维化预防诊断、证候研究、治疗、药物载体等方面提供新的切入点,也会成为推动中医药在肝纤维化防治领域发展与应用的重要研究方向。

中医药调控TGF-β1/Smad信号通路防治肝纤维化的研究概况

肝纤维化是多种慢性肝病进展为肝硬化、肝癌等恶性肝病极其重要的病理过程,肝硬化和肝癌是不可逆的,而肝纤维化却具有不完全可逆性。目前,国内外对肝纤维化的治疗主要是以去除致病因素或对症治疗为主,尚缺乏特异性治疗药物。中医药通过抑制TGF-β1/Smad信号通路的转导,可有效拮抗肝纤维化的发生发展。该综述通过筛选近五年的相关实验研究文献,从TGF-β1/Smad信号通路在肝纤维化中的作用、中医对肝纤维化的认识以及中医药靶向调控TGF-β1/Smad信号通路防治肝纤维化的研究三个方面进行了归纳总结,为该领域研究人员提供中医药思路。

中药活性成分及复方调控JAK/STAT信号通路改善肝纤维化的研究进展

肝纤维化是各种慢性肝损伤的病理过程,若不及时治疗,最终可能导致肝硬化或肝癌。Janus激酶/信号转导及转录激活蛋白(JAK/STAT)信号通路与肝纤维化的发生发展密切相关。本文基于JAK/STAT信号通路总结了中药活性成分及复方改善肝纤维化的研究进展,发现活血化瘀类(如鬼箭羽醇、紫杉醇等成分及二十五味松石丸、肝复康等复方)、清热解毒类(如桦木酸、杠板归总黄酮等成分及片仔癀、克癀胶囊等复方)、疏肝行气类(如秦皮素、葫芦素B等成分及柴胡疏肝散、小柴胡汤等复方)中药活性成分和复方均可通过抑制JAK/STAT信号通路活性,降低炎症反应,抑制肝星状细胞增殖等,发挥改善肝纤维化的作用。

中医利水渗湿法治疗痛风性肾纤维化最新研究进展

纤维化是痛风性肾病进展至终末期肾衰竭的共同通路,中医基于“脾肾亏虚、水湿内停、痰浊结聚、瘀血凝滞”基本病机,以“利水渗湿”为法在治疗和调控痛风性肾纤维化临床疗效显著。本研究以痛风性肾纤维化、痛风性肾病、中医、中药等为关键词,通过中国知网(CNKI)、万方数据库(WF)、重庆维普数据库(VIP)三大中文数据库及PubMed数据库检索近20年相关文献,系统综述痛风性肾纤维化的中医病理机制和具有“利水渗湿”功效中药及复方抗痛风性肾纤维化最新研究进展,旨在为中医“利水渗湿”法治疗痛风性肾纤维化研究提供参考和思路。

新生儿抚触联合中医穴位按摩护理在新生儿黄疸中的应用研究

目的 探究在新生儿黄疸中应用新生儿抚触联合中医穴位按摩护理的效果。方法 以2021年5月—2023年5月为研究开展时段,抽选在该时段内在商丘市第一人民医院分娩出生确诊黄疸的新生儿80例为研究对象,按照电脑随机分组的方式划分40例为对照组,接受常规新生儿抚触护理,余40例患儿为观察组,在对照组的基础上增加中医穴位按摩,比较两组患儿的护理前后经皮胆红素值(TCB)、血清胆红素水平(TB)、血清直接胆红素水平(DB)值、黄疸消退时间、胆红素恢复时间、日睡眠时间、日排便次数、体质量增长。结果 护理后,观察组观察组TCB下降快于对照组(P<0.05);TB、DB均低于对照组(P<0.05);黄疸消失时间、血清胆红素恢复时间均短于对照组(P<0.05);日睡眠时间、日排便次数、体质量均高于对照组(P<0.05)。结论 在新生儿黄疸中应用新生儿抚触联合中医穴位按摩护理的效果较好,可降低血清胆红素水平,改善黄疸症状,加快黄疸消退,保障了新生儿睡眠时间,利于新生儿排便和正常哺育,体质量向正向情况良好发展。

Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue,and also the leading cause of liver-related death worldwide.During the treatment of liver fibrosis,in addition to antiviral therapy or removal of inducers,there remains a lack of specific and effective treatment strategies.For thousands of years,Chinese herbal medicines(CHMs)have been widely used to treat liver fibrosis in clinical setting.CHMs are effective for liver fibrosis,though its mechanisms of action are unclear.In recent years,many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis.There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms.In this review,the role of CHMs in the treatment of liver fibrosis is described,based on studies over the past decade,which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy.Among them,inhibition of stellate cell activation is identified as the most common mechanism.This article provides insights into the research direction of CHMs,in order to expand its clinical application range and improve its effectiveness.