Herbal medicines for the prevention of alcoholic liver disease: A review

Ethnopharmacological relevance

Long-term excess alcohol exposure leads to alcoholic liver disease (ALD)—a global health problem without effective therapeutic approach. ALD is increasingly considered as a complex and multifaceted pathological process, involving oxidative stress, inflammation and excessive fatty acid synthesis. Over the past decade, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of ALD, due to their multiple targets and less toxic side effects. Several herbs, such as Cnidium monnieri (L.) Cusson (Apiaceae), Curcuma longa L. (Zingiberaceae) and Pueraria lobata (Willd.) Ohwi (Leguminosae), etc., have been shown to be quite effective and are being widely used in China today for the treatment of ALD when used alone or in combination.

Aim of the review

To review current available knowledge on herbal medicines used to prevent or treat ALD and their underlying mechanisms.

Materials and methods

We used the pre-set searching syntax and inclusion criteria to retrieve available published literature from PUBMED and Web of Science databases, all herbal medicines and their active compounds tested on ALD induced by both acute and chronic alcohol ingestion were included.

Results

A total of 40 experimental studies involving 34 herbal medicines and (or) active compounds were retrieved and reviewed. We found that all reported extracts and individual compounds from herbal medicines/natural plants could be beneficial to ALD, which might be attributed to regulate multiple critical targets involved in the pathways of oxidation, inflammation and lipid metabolism.

Conclusions

Screening chemical candidate from herbal medicine might be a promising approach to drug discovery for the prevention or treatment of ALD. However, further studies remain to be done on the systematic assessment of herbal medicines against ALD and the underlying mechanisms, as well as their quality control studies.     

低脂饮食及体能锻炼对中年人血清总胆固醇的影响

[目的]研究低脂饮食与体能锻炼对于年龄介于40至55岁的中年男女的血清总胆固醇水平的影响。[方法]年龄介于40-55岁、血清总胆固醇处于高胆固醇边缘的26名男女志愿者为样本研究对象,其体重平均为(67．31±7．75)kg,身高平均为(159．98±5．2)cm。随机分为两组,A组采取低脂饮食,同时进行至少每隔1日30min快步行走的锻炼,持续3个月;B组只采取相同于A组的低脂饮食3个月,不进行任何运动锻炼。两项调查问卷各为社会背景与饮食习惯以及日常体能锻炼的情况。在实验前测定血液指标包括血清总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)以及三酰甘油(TG),实验开始后6周及3个月再次测定上述指标并进行统计分析。[结果]统计分析结果表明A、B两组对象在实验开始前的TC、HDL、LDL、TG值差异均无显著性(均P>0．05)。经过3个月的实验后,A组的TC、HDL、LDL分别为(5．19±0．62)、(1．21±0．52)、(2．58±0．52)mmol/L,较实验前的(6．93±0．33)、(1．85±0．59)、(3．10±0．73)mmol/L均有明显下降,P<0．01或<0．05;B组的TC、LDL分别为(5．88±0．69)、(2．84±0．45)mmol／L,较实验前(7．16±0．56)、(3．43±0．79)mmol／L也有较大下降,P<0．01和<0．05。A组TC值下降比B组更明显,P<0．05。[结论]低脂饮食可以作为中年人减低血清总胆固醇水平的良好膳食疗法,在低脂饮食的同时加强体能锻炼可以使血清胆固醇水平更进一步降低。     

氟伐他汀治疗50例冠心病伴高脂血症的临床疗效分析

目的分析与探讨采用氟伐他汀对冠心病伴高脂血症的治疗效果。方法选取本院2009年8月至2011年8月期间收治的冠心病伴高脂血症患者共50例,对其给予氟伐他汀40mg进行治疗,疗程持续6周,观察患者在治疗前与治疗后的TG、TC、HDL-C、LDL-C以及肝肾功能、血糖值、12导联静息心电图等,观察治疗效果。结果通过6周的治疗后,患者的TC降低有效率为29.0%,TG降低有效率为32.2%,LDL-C降低有效率为30.5%,HDL-C升高有效率为37.0%,治疗前后差异性具有统计学意义。患者合并冠心病的症状在通过6周的治疗后,有明显的好转。结论采用氟伐他汀对冠心病合并高脂血症患者进行治疗疗效良好,不良反应少,值得在临床上进行推广与应用。     

Reelin activates the small GTPase TC10 and VAMP7 to promote neurite outgrowth and regeneration of dorsal root ganglia (DRG) neurons

Axonal outgrowth is a fundamental process during the development of central (CNS) and peripheral (PNS) nervous system as well as in nerve regeneration and requires accurate axonal navigation and extension to the correct target. These events need proper coordination between membrane trafficking and cytoskeletal rearrangements and are under the control of the small GTPases of the Rho family, among other molecules. Reelin, a relevant protein for CNS development and synaptic function in the adult, is also present in the PNS. Upon sciatic nerve damage, Reelin expression increases and, on the other hand, mice deficient in Reelin exhibit an impaired nerve regeneration. However, the mechanism(s) involved the Reelin‐dependent axonal growth is still poorly understood. In this work, we present evidence showing that Reelin stimulates dorsal root ganglia (DRG) regeneration after axotomy. Moreover, dissociated DRG neurons express the Reelin receptor Apolipoprotein E‐receptor 2 and also require the presence of TC10 to develop their axons. TC10 is a Rho GTPase that promotes neurite outgrowth through the exocytic fusion of vesicles at the growth cone. Here, we demonstrate for the first time that Reelin controls TC10 activation in DRG neurons. Besides, we confirmed that the known CNS Reelin target Cdc42 is also activated in DRG and controls TC10 activity. Finally, in the process of membrane addition, we found that Reelin stimulates the fusion of membrane carriers containing the v‐SNARE protein VAMP7 in vesicles that contain TC10. Altogether, our work shows a new role of Reelin in PNS, opening the option of therapeutic interventions to improve the regeneration process.     

Bile salt-induced apoptosis involves NADPH oxidase isoform activation

BACKGROUND & AIMS: Hydrophobic bile salts trigger a rapid oxidative stress response as an upstream event of CD95 activation and hepatocyte apoptosis. METHODS: The underlying mechanisms were studied by Western blot, immunocytochemistry, protein knockdown, and fluorescence resonance energy transfer microscopy in rat hepatocytes and human hepatoma cell line 7 (Huh7). RESULTS: The rapid oxidative stress formation in response to taurolithocholate-3-sulfate (TLCS) was inhibited by diphenyleneiodonium, apocynin, and neopterin, suggestive for the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. TLCS induced a rapid serine phosphorylation of the regulatory subunit p47phox, which was sensitive to inhibition of sphingomyelinase and protein kinase Czeta (PKCzeta). Inhibitors of p47phox phosphorylation and p47phox protein knockdown abolished the TLCS-induced oxidative stress response and blunted subsequent CD95 activation. Consequences of TLCS-induced oxidative stress were c-Jun-N-terminal kinase activation and Yes-dependent activation of the epidermal growth factor receptor (EGFR), followed by EGFR-catalyzed CD95 tyrosine phosphorylation, formation of the death-inducing signaling complex, and execution of apoptosis. As shown by fluorescence resonance energy transfer experiments in Huh7 cells, TLCS induced a c-Jun-N-terminal kinase-dependent EGFR/CD95 association in the cytosol and trafficking of this protein complex to the plasma membrane. Inhibition of EGFR tyrosine kinase activity by AG1478 allowed for cytosolic EGFR/CD95 association, but prevented targeting of the EGFR/CD95 complex to the plasma membrane. Both processes, and TLCS-induced Yes and EGFR activation, were sensitive to inhibition of sphingomyelinase, PKCzeta, or NADPH oxidases. CONCLUSIONS: The data suggest that hydrophobic bile salts activate NADPH oxidase isoforms with the resulting oxidative stress response triggering activation of the CD95 system and apoptosis.     

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats

The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ⁹-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ⁹-THC treated, (3) diabetic, and (4) diabetic + Δ⁹-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ⁹-THC and Δ⁹-THC treated diabetic groups received 3 mg/kg/day of Δ⁹-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin–biotin–peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic + Δ⁹-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic + Δ⁹-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes + Δ⁹-THC group showed a decrease compared to the diabetic group. These results indicate that Δ⁹-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.     

Cholesterol in midlife increases the risk of Alzheimer's disease during an up to 43-year follow-up

PurposeVascular risk factors in midlife may play a role in the development of cognitive decline, dementia and Alzheimer’ disease (AD). The role of serum total cholesterol has yielded inconsistent results in diverse cohorts.ObjectiveTo analyze the relationship between the midlife cholesterol level and AD in late life in a homogenous cohort of Caucasian men.MethodsThe Helsinki Businessmen Study is a cohort of male business executives who have been followed-up since 1964. Midlife cholesterol level was available in 3293 men, of whom 205 developed a register-verified AD. Cognitively intact men in 2007 (n = 844) served as controls, and logistic regression adjusted for age and cardiovascular risk factors was used to investigate the association between cholesterol and AD.ResultsAt baseline, the men with subsequent AD diagnosis had 0.4 mmol/L higher total cholesterol level than controls (6.7 vs 6.3 mmol/L). In adjusted analyses 1 mmol/L rise in total cholesterol was associated with a 22% increased risk of AD (odds ratio [OR] 1.22, 95% confidence interval 1.06 to 1.40, P = 0.005). Risk of AD (OR with 95% CI) also increased in a stepwise manner from the lowest to highest quartile of midlife cholesterol from 1.0 (referent) to 1.6 (1.01–2.6), 1.9 (1.2–3.0), and 2.0 (1.2–3.3), respectively.ConclusionIn this longitudinal study with up to 43 years of follow-up, higher serum total cholesterol in early midlife was clearly associated with a higher risk of AD in late life.     

心脑清软胶囊联合匹伐他汀治疗高脂血症的临床研究

目的探讨心脑清软胶囊联合匹伐他汀治疗高脂血症的临床疗效。方法选取2017年7月—2018年7月在河北省第七人民医院进行治疗的88例高脂血症患者,根据住院号的奇偶数分为对照组和治疗组,每组各44例。对照组饭后口服匹伐他汀钙片,1片/次,1次/d。治疗组在对照组治疗基础上饭后口服心脑清软胶囊,2粒/次,3次/d。两组均治疗8周后进行效果比较。观察两组的临床疗效,比较两组治疗前后血脂指标、肥胖指标、血清学指标和氧化应激指标的变化情况。结果治疗后,对照组和治疗组的总有效率分别是81.82%、93.18%,两组比较差异具有统计学意义(P0.05)。治疗后,两组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均较治疗前显著降低,而高密度脂蛋白胆固醇(HDL-C)水平均增高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组TC、TG、LDL-C水平显著低于对照组,而HDL-C水平高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组体质量、肥胖度、体质量指数、体脂率都明显下降,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组这些肥胖指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组超敏C反应蛋白(hs-CRP)、肿瘤坏死因素-α(TFN-α)、干扰素-γ(IFN-γ)、嗜酸粒细胞阳离子蛋白(ECP)、总氧化态(TOS)水平均较治疗前显著下降,而总抗氧化态(TAS)和对氧磷酶-1(PON1)表达水平均增高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组hs-CRP、TFN-α、IFN-γ、ECP、TOS水平低于对照组,而TAS和PON1表达水平均高于对照组,两组比较差异具有统计学意义(P0.05)。结论心脑清软胶囊联合匹伐他汀治疗高脂血症具有较好的临床疗效,可有效降低血脂水平和肥胖指标,改善机体炎症反应,改善机体氧化应激状态,具有一定的临床推广应用价值。