Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions,biological properties and clinical efficacy

Context: Cardiometabolic risks are regarded as the crucial factors associated with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an increased attention to medicinal plants in the current healthcare system, the effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have been consecutively considered in scientific research.

Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks.

Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed.

Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects.

Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses.     

曾定伦治疗高脂血症经验

曾定伦主任中医师认为高脂血症属虚实夹杂之证,与气血运行密切相关,其病理产物不外乎"痰浊""瘀血""水饮"等,与日常饮食、生活习惯、体质和某些基础疾病(高血压、消化系统疾病、内分泌疾病)密切相关。高脂血症病因主要有:受纳过剩、内伤饮食,缺乏运动,先天禀赋,久病体虚、脏腑功能失调,情志失调。其治疗重点当紧抓三个重点:节食限食、减少食物摄入,调理五脏,增加脂浊的消耗。曾老师认为痰浊瘀血是形成脂膏的关键,是高脂血症发病的病理基础,一则脾失布津,聚湿成痰,形成脂膏,一则水液代谢失常,痰浊堆积,脂膏留滞,再则气机不畅,气滞血瘀,瘀血凝结,形成脂膏。曾老师以"痰瘀"立论治疗高血脂,研制出验方"十味降脂片",对于调整各种类型脂肪代谢异常具有良好功效。     

李应东教授从脾气虚论治高脂血症

李应东教授认为脾胃气虚,脾失健运导致膏脂生成及转运输布异常是高脂血症发病的关键,脾气虚形成的痰浊、血瘀作为病理产物和致病因子贯穿疾病始终,以脾气虚为本,痰浊、血瘀为标,治疗上以益气健脾,化痰祛瘀为主,方选四君子汤、二陈汤及桃红四物汤随症加减治疗。     

The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy

Abstract. Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol +1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak= 11.52 ±1.09 mmol 1^-1 vs. 4.73 ± 0.31 on control diet, < 0.001) and triglyceride concentrations (peak = 2.31 ± 0.27 mmol 1^-1 vs. 1.41 ±0.29, <0.05) and a marked increase in βmigrating lipoproteins. The severity of hypercholester-olaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, < 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, <0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (<0.05). The kidney total cholesterol content was increased from 29.2 ±0.8 to 47.7 ± 3.3 μmols g^-1 dry weight (<0.0001), with esterified cholesterol increasing from 7.5 ± 0.4% to 14.5 ± 2.1% of total (<0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition ( r _s= 0.7195, <0.0001) and tissue total cholesterol content ( r _s= 0.6053, <0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable.     

Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy: studies in type IIA and type IIb hyperlipoproteinaemia

The effects of lipid lowering therapy (bezafibrate) on plasma lipoproteins was investigated in twelve patients with familial hypercholesterolaemia (type IIA) and eight with familial combined hyperlipidaemia (type IIB). Bezafibrate caused a decrease of plasma cholesterol, plasma triglycerides, plasma apolipoprotein B, VLDL cholesterol and LDL cholesterol and an increase of HDL cholesterol. Post-heparin plasma lipoprotein and hepatic lipase activities increased in both groups (significant only in type IIB). Lipoprotein composition showed the following changes: Increased protein and phospholipids and decreased triglycerides and cholesteryl esters in VLDL. Decreased protein and triglycerides and increased free and esterified cholesterol in LDL. Decreased triglycerides and increased phospholipids in HDL. Cholesteryl ester to protein ratios decreased in VLDL and increased in LDL. The hydrated density of LDL (both groups) and of HDL3 (type IIB) decreased following bezafibrate therapy. These changes were in general similar to those observed in hypertriglyceridaemic patients and could be ascribed, at least in part, to the increase of plasma lipase activities and the decrease of lipid transfer reactions. Comparing the present data with that previously reported, it was found that bezafibrate caused decreased LDL cholesterol in types IIA and IIB but increased levels in type IV. This change was correlated with the initial plasma triglycerides (r = 0.74, P less than 0.0001) and initial plasma LDL cholesterol (r = 0.66, P less than 0.001). It is concluded that varied response of LDL to therapy reflects a complex interaction of metabolic events, including changing rates of VLDL conversion to LDL, lipoprotein compositional changes and effects of therapy on LDL degradation rates.     

Multifactorial treatment of hypertensive men at high cardiovascular risk and low-density lipoprotein cholesterol affinity to human arterial proteoglycans

The purpose of this work was to examine in an open, randomized parallel-group study whether an intervention programme directed towards hypercholesterolaemia, smoking and diabetes mellitus in treated hypertensive men was associated with less complex formation between low-density lipoprotein (LDL) and human arterial proteoglycans than was the case with usual care. The intervention consisted mainly of non-pharmacological treatment, but drug therapy could be instituted to achieve the treatment goals in the intervention group. The intervention programme was associated with a significant reduction in body mass index, and 46% of the patients were on lipid-lowering medication at the follow-up examination. The net differences were (intervention − usual care): change in serum LDL-cholesterol, −0.48 mmol L⁻¹ (95% confidence interval −0.84 to −0.11 mmol L⁻¹), precipitated LDL-cholesterol, −5.5 μg (95% CI −9.0 to −1.1 μg). The latter remained after adjustment for the difference in serum LDL-cholesterol between the groups. Our conclusion is that the multifactorial risk factor treatment programme was associated with a reduced tendency of LDL to form complexes with human arterial proteoglycans.     

Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate

Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor to the development of glucose intolerance, dyslipidaemia and hypertension in non-insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle, consumption of energy-rich diet, obesity, longer lifespan, etc., are important reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS) and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical setting. As no work has been carried out so far to assess the effect of PM, OS and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia, we undertook this study to assess whether these extracts attenuate the metabolic alteration induced by fructose-rich diet in rats. Five groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200 mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days. Fructose feeding to normal rats for 30 days significantly increased serum glucose, insulin and triglyceride levels in comparison with control. Treatment with all the three plants extract for 30 days significantly lowered the serum glucose levels in comparison with control group. However, only PM extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and FG had no significant effect on these parameters. Results of this study, in addition to previous clinical benefits of PM seen in NIDDM subjects, are suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the associated disorder of type 2 diabetes; however, OS and FG may not be useful. Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and pterostilbene) have been identified in the PM, yet future studies are required to certify their efficacy and safety before clinical scenario.     

The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations

OBJECTIVES: Ritonavir (RTV) at doses of 400 mg twice a day (bid) or higher adversely affects serum lipids. However, the effect of RTV 100 mg bid on serum lipids is unknown. We conducted a study to evaluate the effect of RTV 100 mg bid on fasting serum lipid profiles in HIV-negative healthy volunteers. METHODS: Ritonavir 100 mg bid was administered for 14 days to 20 healthy HIV-seronegative adults with normal serum lipids. After a 7-day washout, lopinavir/ritonavir (LPV/RTV) 400/100 mg bid was administered for 14 days. Fasting serum lipid parameters were measured twice at baseline, after 14 days of RTV, and after 14 days of LPV/RTV, and comparisons were made at each time-point for levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, the total/HDL cholesterol ratio and triglycerides. RESULTS: After 14 days of RTV 100 mg bid, total cholesterol level increased by 10.2% (P<0.001), LDL cholesterol level increased by 16.2% (P<0.001), triglyceride levels increased by 26.5% (P<0.001), HDL cholesterol level decreased by 5.4% (P<0.01) and the total/HDL cholesterol ratio increased by 17.3% (P<0.001). The addition of LPV 400 mg bid to RTV 100 mg bid resulted in no significant further changes in LDL cholesterol or triglyceride level or total/HDL cholesterol ratio, but there were significant increases in both total cholesterol (8.0% increase; P=0.007) and HDL cholesterol levels (6.7% increase; P=0.008). CONCLUSIONS: Ritonavir dosed at 100 mg bid significantly increased the concentration of total cholesterol, LDL cholesterol, total/HDL cholesterol ratio and triglycerides and reduced HDL cholesterol concentration. The addition of LPV 400 mg bid to RTV 100 mg bid further increased both total and HDL cholesterol levels without affecting the total/HDL ratio.