Efficacy and safety of herbal medicines in treating gastric ulcer: A review

Gastric ulcer is a common disorder of the digestive system.Current therapeutic regimens largely rely on Western medicine.However,numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms.This review updates the efficacy and safety of herbal medicines in treating gastric ulcer,and the mechanisms of their action in humans and animal models.Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models,and herbal medicines display fewer adverse effects.The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation,anti-oxidation,and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity.Some herbal medicines also exhibit antimicrobial properties.Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively,with few adverse effects.     

Of mice and men: Is there a future for metformin in the treatment of hepatic steatosis?

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases, of which the first stage is steatosis. It is one of the most common liver diseases in developed countries and there is a clear association between type 2 diabetes (T2DM) and NAFLD. It is estimated that 70% of people with T2DM have NAFLD and yet there is currently no licensed pharmacological agent to treat it. Whilst lifestyle modification may ameliorate liver fat, it is often difficult to achieve or sustain; thus, there is great interest in pharmacological treatments for NAFLD. Metformin is the first-line medication in the management of T2DM and evidence from animal and human studies has suggested that it may be useful in reducing liver fat via inhibition of lipogenesis and increased fatty acid oxidation. Findings from the majority of studies undertaken in rodent models clearly suggest that metformin may be a powerful therapeutic agent specifically to reduce liver fat accumulation; data from human studies are less convincing. In the present review we discuss the evidence for the specific effects of metformin treatment on liver fat accumulation in animal and human studies, as well as the underlying proposed mechanisms, to try and understand and reconcile the difference in findings between rodent and human work in this area.     

Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD)/nonalcoholic steatohepatitis(NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers(thiazolidinediones) and antioxidants(vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH.     

Hepatic fat as clinical outcome and therapeutic target for nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of advanced liver disease in Western countries. NAFLD is defined in the presence of increased hepatic fat content, which is mainly stored under the form of neutral lipids within intracellular droplets and is not explained by at risk alcohol intake. In order to understand the pathogenesis, monitor the progression and find novel treatments for this condition, previous research efforts mainly addressed the role of inflammation. However, very recent data seem to suggest that hepatic lipid accumulation may be involved in NAFLD pathogenesis by driving secondary inflammation and fibrosis progression. Here, we will briefly review the novel results derived from natural history, genetics, imaging studies and therapeutic trials that support the notion that hepatic fat accumulation may represent a major clinical outcome and therapeutic target for NAFLD. Indeed, prospective and genetic data are consistent with hepatic fat being a driver of NAFLD progression. Furthermore, new technologies will render possible to monitor hepatic fat content without the need of invasive assessment, thereby allowing to identify patients at higher risk, and to monitor the response to drugs that act by decreasing hepatic lipid accumulation.     

化痰祛湿疏肝方联合辛伐他汀治疗非酒精性脂肪性肝病痰湿内阻证患者临床疗效研究

目的 观察应用化痰祛湿疏肝方联合辛伐他汀治疗非酒精性脂肪性肝病(NAFLD)痰湿内阻证患者的临床疗效。方法 2020年2月～2022年1月我院诊治的符合中医痰湿内阻证的68例NAFLD患者,其中33例接受辛伐他汀治疗,另35例在上述治疗的基础上联合化痰祛湿疏肝方治疗,两组均治疗观察12 w。采用硫化巴比妥酸法和氧化酶法检测血清丙二醛(MDA)和超氧化物歧化酶(SOD)水平,使用彩色多普勒超声检测肝脏脂肪含量(LFC)。结果 在治疗结束时,中西药联合治疗组临床有效率为94.3%,显著高于辛伐他汀治疗组的75.8%(P<0.05);中西药联合治疗组右胁胀闷、周身困重、大便粘滞、倦怠无力和脘腹胀满的中医症候积分分别为(1.4±0.5)分、(0.9±0.2)分、(0.8±0.2)分、(1.2±0.4)分和(1.5±0.3)分,显著低于辛伐他汀治疗组[分别为(2.8±0.7)分、(2.1±0.3)分、(1.5±0.4)分、(2.1±0.6)分和(2.4±0.6)分,P<0.05];中西药联合治疗组肝功能和血清指标改善显著优于辛伐他汀治疗组(P<0.05);中西药联合治疗组血清M...     

Optimal management for alcoholic liver disease: Conventional medications,natural therapy or combination?

Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.     

Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is one of the leading causes of chronic liver diseases around the world due to the modern sedentary and food-abundant lifestyle, which is characterized by excessive fat accumulation in the liver related with causes other than alcohol abuse. It is widely acknowledged that insulin resistance, dysfunctional lipid metabolism, endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis/necrosis may all contribute to NAFLD. Autophagy is a protective self-digestion of intracellular organelles, including lipid droplets(lipophagy), in response to stress to maintain homeostasis. Lipophagy is another pathway for lipid degradation besides lipolysis. It is reported that impaired autophagy also contributes to NAFLD. Some studies have suggested that the histological characteristics of NAFLD(steatosis, lobular inflammation, and peri-sinusoid fibrosis) might be improved by treatment with traditional Chinese herbal extracts, while autophagy may be induced. This review will provide insights into the characteristics of autophagy in NAFLD and the related role/mechanisms of autophagy induced by traditional Chinese herbal extracts such as resveratrol, Lycium barbarum polysaccharides, dioscin, bergamot polyphenol fraction, capsaicin, and garlic-derived S-allylmercaptocysteine, which may inhibit the progression of NAFLD. Regulation of autophagy/lipophagy with traditional Chinese herbal extracts may be a novel approach for treating NAFLD, and the molecular mechanisms should be elucidated further in the near future.     

高尿酸血症与非酒精性脂肪性肝病

非酒精性脂肪性肝病是由于肝脏中脂肪过度沉积,诱发炎性反应以及氧化应激损伤的一组疾病.而尿酸是人类嘌呤代谢的终产物,在体内起到抗氧化、调节免疫功能等生理作用.越来越多的证据表明高尿酸血症与非酒精性脂肪性肝病有关.不论是横断面研究还是前瞻性研究均显示高尿酸血症是非酒精性脂肪性肝病的独立危险因素.高尿酸血症可成为机体的致炎因子,诱导胰岛素抵抗,激发炎性反应信号通路,诱导炎性因子的产生,导致肝细胞中脂肪的积聚和炎性损伤.降尿酸治疗可对肝脏起到保护作用,可能成为非酒精性脂肪性肝病的治疗手段.     

Liver fat as risk factor of hepatic and cardiometabolic diseases

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive accumulation of fat in the liver that can progress to liver inflammation (non-alcoholic steatohepatitis [NASH]), liver fibrosis, and cirrhosis. Although most efforts for drug development are focusing on the treatment of the latest stages of NAFLD, where significant fibrosis and NASH are present, findings from studies suggest that the amount of liver fat may be an important independent risk factor and/or predictor of development and progression of NAFLD and metabolic diseases. In this review, we first describe the current tools available for quantification of liver fat in humans and then present the clinical and pathophysiological evidence that link liver fat with NAFLD progression as well as with cardiometabolic diseases. Finally, we discuss current pharmacological and non-pharmacological approaches to reduce liver fat and present open questions that have to be addressed in future studies.     

Herbal medicine-related hepatotoxicity

Herbal medicine products represent a common therapeutic approach in the East and are gaining increasing popularity in Western countries. They are unjustifiably considered to be side-effect free; on the contrary, severe toxicity, including catastrophic hepatic injury has been reported in association with their use. Vigilance is required from both physicians and the general public. Physicians should always suspect herbal medicines when evaluating a patient with unexplained liver injury. Regulation standards for herbal products need to be reconsidered, so that the efficacy and safety of these products have been clearly demonstrated before they enter the markets.     

关于农村“混合型社区”管理的思考

在党的十七大和十七届三中全会关于加快形成城乡经济社会发展一体化新格局精神的指引下,城乡一体化发展综合配套改革正在很多地方如火如荼地展开。随着城乡一体化进程的加快,大量农民向城镇和新型社区集聚,形成了一大批农民集中居住的"混合型社区"。混合型社区是新兴城市和一些县级城市社区的特有模式,是城市化建设过程中的一个过渡形式。探索"混合型社区"管理模式,确保城乡一体化顺利推进,既是城市化发展亟需研究和解决的重要课题,也是确保农村和谐稳定的迫切需要。     

NAFLD in the absence of metabolic syndrome: different epidemiology, pathogenetic mechanisms, risk factors for disease progression?

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that have been associated with an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Insulin resistance and central obesity are the key components of MetS, ultimately leading to liver fat accumulation and the subsequent development of necroinflammatory liver injury. However, the origin and nature of the metabolic stressors responsible for stimulating the progression of simple steatosis to nonalcoholic steatohepatitis (NASH) remain to be clearly identified. In addition, epidemiologic research on the association between MetS and NAFLD has provided only limited information to guide the development of targeted interventions, in particular, nutrition and pharmacologic prevention programs. This review summarizes the evidence supporting the proposal that NAFLD is not invariably associated with the presence of MetS, and mechanisms other than insulin resistance may contribute to the chronic inflammatory processes that underpin the development of liver fat accumulation and the subsequent architectural distortion of the liver. A special focus is given to increased hemoglobin as a risk factor for the development of NAFLD in the absence of MetS.     

Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.     

Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver disease worldwide. NAFLD progresses in some cases to non-alcoholic steatohepatitis (NASH), which is characterized, in addition to liver fat deposition, by hepatocyte ballooning, inflammation and liver fibrosis, and in some cases may lead to hepatocellular carcinoma. NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus (T2DM). Currently, lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used in the management of T2DM and do not have major side effects like hypoglycemia. In patients with NAFLD, the GLP-1 receptor production is down-regulated. Recently, several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation, alleviating the inflammatory environment and preventing NAFLD progression to NASH. In this review, we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH. Finally, as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD, we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.     

Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease:The search for alternative causative factors

The incidence and prevalence of non-alcoholic fatty liver disease(NAFLD)is constantly increasing.Despite this is apparently associated with the growing increase in obesity,insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fatin the liver.Conversely,NAFLD is a predictor of other metabolic risks.NAFLD is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and endstage liver disease.Consequently,the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful consideration.Mitochondria are possible targets as these organelles generate energy from nutrient oxidation.Some findings,generated in patients with extreme obesity and in murine models,support the notion that NAFLD could be a mitochondrial disease.This is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation,the production of reactive oxygen species,the release of cytokines causing inflammation and cell death.Here we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative stress.Their combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets.     

Prevention of free fatty acid-induced hepatic lipotoxicity by 18beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and affects millions of people worldwide. Despite the increasing prevalence of NAFLD, the exact molecular/cellular mechanisms remain obscure and effective therapeutic strategies are still limited. It is well-accepted that free fatty acid (FFA)-induced lipotoxicity plays a pivotal role in the pathogenesis of NAFLD. Inhibition of FFA-associated hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has a variety of pharmacological properties including anti-inflammatory, antioxidant, and immune-modulating activities. GL has been used to treat hepatitis to reduce liver inflammation and hepatic injury; however, the mechanism underlying the antihepatic injury property of GL is still poorly understood. In this report, we provide evidence that 18 beta-glycyrrhetinic acid (GA), the biologically active metabolite of GL, prevented FFA-induced lipid accumulation and cell apoptosis in in vitro HepG2 (human liver cell line) NAFLD models. GA also prevented high fat diet (HFD)-induced hepatic lipotoxicity and liver injury in in vivo rat NAFLD models. GA was found to stabilize lysosomal membranes, inhibit cathepsin B expression and enzyme activity, inhibit mitochondrial cytochrome c release, and reduce FFA-induced oxidative stress. These characteristics may represent major cellular mechanisms, which account for its protective effects on FFA/HFD-induced hepatic lipotoxicity. CONCLUSION: GA significantly reduced FFA/HFD-induced hepatic lipotoxicity by stabilizing the integrity of lysosomes and mitochondria and inhibiting cathepsin B expression and enzyme activity.     

Role of cytokines and chemokines in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.     

Hypertransaminasemia and severe hepatic steatosis without inflammation. A case report

Nonalcoholic fatty liver disease (NAFLD) is a medical condition that may progress to end-stage liver disease. The spectrum of NAFLD is wide and ranges from simple fat accumulation in hepatocytes (steatosis), to fat accumulation plus necroinflammatory activity with or without fibrosis (steatohepatitis). In addition, NAFLD is the most common cause of abnormal liver-test results among adults with a prevalence of 13%-23%. This case report is an example of a patient with asymptomatic hypertransaminasemia and severe hepatic steatosis without inflammation in which the diagnosis was made by liver biopsy.     

Nonmedicinal interventions in nonalcoholic fatty liver disease

Unhealthy diet and lack of physical exercise are responsible for fat accumulation in the liver, which may lead to liver disease. Histologically, the severity of the disease has two stages: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD is defined by the presence of steatosis with no evidence of cellular injury such as hepatocyte ballooning. NASH is a distinct entity from NAFLD, and is characterized by the presence of inflammation with hepatocytes damage, with or without fibrosis. While several therapeutic strategies have been proposed to improve this condition, the present review aims to discuss nonmedicinal interventions used to reduce liver involvement or to prevent the disease altogether. The authors investigated dietary patterns and vitamin deficiencies associated with NAFLD, and their role in enhancing disease severity. Additionally, they reviewed the role of exercise and the use of interventions, such as as intragastric balloon and bariatric surgery, for improving disease progression. The authors propose monitoring disease progression or repair by following changes in cytoadipokine levels.