The sensory nitrergic nature of the hepatic insulin sensitizing substance mechanism in conscious rabbits

Functional deterioration of sensory fibres in the anterior hepatic plexus or intraportal administration of 7-nitro indazole (1 mg/kg), a selective inhibitor of neural nitric oxide (NO) synthase, caused insulin resistance as determined by hyperinsulinaemic (100 micro U/ml) euglycaemic (5.5 mmol/l) glucose clamping in chronically instrumented conscious rabbits. Intraportal nitroglycerin restored insulin sensitivity in either case. We conclude that NO of sensory neural origin plays a major role in endogenous neurogenic insulin sensitizing mechanisms.     

葛根素增强胰岛素抵抗-高血压大鼠胰岛素敏感性作用机制研究

目的观察葛根素对胰岛素抵抗—高血压大鼠胰岛素敏感性的作用及其机制。方法用喂饲高脂高糖高盐的方法建立胰岛素抵抗—高血压(IRH)病理模型,随机分为模型卡托普利组(Cap)、葛根素注射液(Pue)高、中、低三个剂量组、模型阴性对照组及正常空白对照组,分别给药后,测定大鼠血压、血清的甘油三酯(TG)、胆固醇(TC)、肿瘤坏死因子-α(TNF-α)、空腹血浆血糖(FPG)及胰岛素(F ins)含量的变化,并计算胰岛素敏感指数(ISI)。结果模型组的血压、血糖、Ins均有显著升高,ISI降低(P<0.05~0.01);Cap和Pue 80mg.kg-1组能降低TNF-α含量,纠正IRH大鼠高胰岛素血症(P<0.05~0.01),提高低下的ISI,差异有高度显著性(P<0.01);而Pue其余两个剂量组,对F ins、TNF-α含量和ISI作用,差异均未见显著性(P>0.05)。Cap和Pue 80mg和40mg.kg-1组,均能降低IRH大鼠TG,TC(P<0.05~0.01);Pue 20mg.kg-1组对上述各指标,则差异均未见显著性(P>0.05)。结论Pue增强胰岛素抵抗-高血压大鼠胰岛素敏感性和降血压,改善胰岛素抵抗可能是通过减少TNF-α分泌,改善脂质代谢,葡萄糖分解等途径实现的。     

葛根素增强胰岛素抵抗-高血压大鼠胰岛素敏感性作用机制研究

OBJECTIVE To observe the effects of puerarin injection(Pue) on insulin sensitivity in insulin resistant hypertensive(IRH) rats.METHODS By feeding high fat-sugar-salt diet to set up the rat model of IRH.Five groups were designed: Captopril,Pue high dose,me     

A new paradigm for diabetes and obesity: the hepatic insulin sensitizing substance (HISS) hypothesis

The glucose disposal effect of insulin after a meal is accounted for in approximately equal measure by the direct action of insulin and the action of HISS (hepatic insulin sensitizing substance) released from the liver and acting on skeletal muscle to stimulate glucose storage as glycogen. The ability of insulin to cause HISS release is determined by hepatic parasympathetic nerves. Eliminating the parasympathetic signal by surgical denervation of the liver or by blockade of hepatic muscarinic receptors, hepatic nitric oxide synthase, or hepatic cyclooxygenase results in insulin resistance that can be accounted for by the absence of HISS action and is referred to as HISS-dependent insulin resistance (HDIR). Animal models in which the insulin resistance has been shown to be HDIR includes the spontaneously hypertensive rat, sucrose fed rats, animals with liver disease, adult offspring of fetal alcohol exposure, acute stress, and ageing. We suggest that HDIR accounts for the major metabolic disturbances in type 2 diabetes, including the postprandial hyperglycemia that results in the majority of pathologies related to diabetes. The observation of meal-induced insulin sensitization (MIS) and the role of HISS allows for consideration of a new paradigm relating meal processing, diabetes, obesity, and insulin resistance. New diagnostic approaches and therapeutic targets are described.     

Intrathecal administration of substance P enhances cutaneous plasma protein extravasation in pentobarbital anaesthetized rats

In pentobarbital-anaesthetized rats, the intrathecal administration of substance P (SP) at T9 spinal cord level enhances plasma protein extravasation (PE) in cutaneous tissues of the back, the hind paws and the ears. This vascular response is maximum at 15 min after administration of SP (6.5 nmol), and the most striking in the skin of the hind paws. Contrary to SP, neurotensin (NT) administered intrathecally failed to enhance PE. Both peptides are however potent enhancers of PE following intravenous injection. PE elicited by intrathecal administration of SP is significantly reduced in both spinal rats and in capsaicin treated animals. These results suggest that SP but not NT may play a role as a spinal chemical mediator in peripheral vascular permeability through a supraspinal reflex mechanism involving sensory afferents.     

The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo.

Thiazolidinediones (TZDs) such as rosiglitazone are antidiabetic peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPARgamma agents improve diabetes by increasing insulin sensitivity and enhancing the differentiation of preadipocytes into adipocytes. The present study aimed to identify if 1-(4-chlorobenzoyl)-5-hydroxy-2-methyl-3-indoleacetitic acid (GY3), a newly synthesized indole compound, could enhance adipocytes differentiation and insulin sensitivity. The results showed that both GY3 and rosiglitazone significantly increased the lipid accumulating of 3T3-L1 adipocytes induced by isobutylmethylxanthine, dexamethasone and insulin mixture, but GY3 (not rosiglitazone) failed to increase the lipid accumulation when induced by insulin alone. In addition, GY3- or rosiglitaozne-induced protein expression of GLUT4 and adiponectin was determined by Western blot analysis. GY3 activated PPARalpha weakly but did not affect PPARgamma, while rosiglitazone activated PPARgamma significantly, suggesting different mechanisms between GY3 and rosiglitazone on adipocyte differentiation. Furthermore, both GY3 and rosiglitazone enhanced the adiponectin and insulin pathway proteins expression and adiponectin secretion in mature adipocytes, but only GY3 not rosiglitazone elevated gene expression of leptin and resistin. Both GY3 and rosiglitazone enhanced glucose consumption in HepG2 cells especially in the presence of insulin. In the in vivo study, GY3 decreased serum glucose and insulin in db/db mice, indicating the insulin sensitizing effect might contribute to its antidiabetic mechanism. Altogether, these results suggest that GY3 could improve insulin resistance and lower glucose level, GY3 and its derivatives might be developed as a substitution therapy for diseases with insulin resistance.     

Guanethidine-induced acute hypersensitivity to noradrenaline in anaesthetized rats

The changes in mean arterial blood pressure, heart rate and the respective noradrenaline dose-response curves after guanethidine sulphate (0.25, 1.25, 5, 20, and 40 mg/kg given intravenously) were studied in chloralose-urethane anesthetized adult rats. After transient changes a dose-dependent maximum fall of the blood pressure was observed 15 minutes after the administration of guanethidine. A fall in heart rate was observed after guanethidine sulphate 0.25 mg/kg, whereas 1,25, 5, 20, and 40 mg/kg initially increased the heart rate followed by a decrease to subnormal levels with minimum values 6-24 hours after guanethidine. Normalization of blood pressure and heart rate occurred within 24 hours and 96 hours, respcetively. Maximum dose-dependent enhancement of changes in blood pressure by noradrenaline 0.5 mug/kg was obtained approximately 15 minutes after guanethidine. Following guanethidine 40 mg/kg the response was increased by a factor 2, and normalization occurred within 96 hours. Fifteen minutes after guanethidine, significant changes in the response of the heart rate to noradrenaline 0.5 mug/kg were obtained with guanethidine 1.25, 5, and 20 mg/kg, whereas fully developed hypersensitivity after 20 and 40 mg/kg did not occur until 6-24 hours later. Following guanethidine 40 mg/kg the response was increased by a factor of 3, and normalization was observed after 96 hours. The present investigation has demonstrated different time-dependent patterns of the effect of guanethidine on blood pressure and heart rate responses to noradrenaline.     

NEU-P11, a novel melatonin agonist,inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats

Evidences indicate that a complex relationship exists among sleep disorders, obesity and insulin resistance. NEU-P11 is a novel melatonin agonist used in treatment of psychophysiological insomnia, and in animal studies NEU-P11 showed sleep-promoting effect. In this study, we applied NEU-P11 on obese rats to assess its potential melatoninergic effects in vivo. Obese models were established using high-fat/high-sucrose-fed for 5 months. NEU-P11 (10 mg/kg)/melatonin (4 mg/kg)/vehicle were administered by a daily intraperitoneal injection respectively for 8 weeks. Our results showed that NEU-P11 or melatonin inhibited both body weight gain and deposit of abdominal fat with no influence on food intake. The impaired insulin sensitivity and antioxidative potency were improved and the levels of plasma glucose, total cholesterol (TC), triglycerides (TG) decreased with an increased in HDL-cholesterol (HDL-c) after NEU-P11 or melatonin administration. These data suggest that NEU-P11, like melatonin, decreased body weight gain and improved insulin sensitivity and metabolic profiles in obese rats. We conclude that NEU-P11 has a melatoninergic effect on regulating body weight in obese rats and also improving metabolic profiles and efficiently enhancing insulin sensitivity.     

Changes in blood glucose and plasma insulin levels induced by bradykinin in anaesthetized rats.

1. The influence of bradykinin (BK) on blood glucose and plasma insulin levels was investigated in anaesthetized rats. 2. Blood glucose level was dose-dependently increased by intravenous infusion of BK. This effect of BK was enhanced by captopril, an inhibitor of angiotensin-converting enzyme (ACE). Des-Arg9-bradykinin (DABK), a kinin B1 receptor agonist, did not modify blood glucose levels while the effect of BK was inhibited by Hoe-140, a kinin B2 receptor antagonist. 3. The effect of BK was reduced by the NO-synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), and by the cyclo-oxygenase inhibitor, indomethacin. The effect of BK was suppressed by the association of propranolol with phentolamine or phenoxybenzamine. It was also reduced by hexamethonium, a ganglion-blocking drug. In adrenalectomized rats, the infusion of BK slightly decreased blood glucose levels. 4. The hyperglycaemic effect of adrenaline was suppressed by propranolol associated with phentolamine or phenoxybenzamine, but it was not modified by L-NAME. 5. Infusion of BK did not modify plasma insulin levels. However, after phentolamine and propranolol, BK induced a transient 2 fold rise in plasma insulin levels. The release of insulin was dose-dependent and inhibited by Hoe-140. 6. We conclude that infusion of BK induces, via a stimulation of B2 receptors, the release of NO and of prostanoids. The latter agents activate through a reflex pathway the release of catecholamines from the adrenal medulla. This release increases blood glucose levels and reduces plasma insulin levels. After adrenoceptor inhibition, BK induces a secretion of insulin, via the stimulation of B2 receptors.     

Inhaled insulin: a novel route for insulin delivery

Insulin has been in use for the treatment of patients with diabetes mellitus for over 75 years. However, despite the known benefits of tight glycaemic control, multiple insulin injections have still not gained widespread clinical acceptance. Although there have been attempts to find effective non-invasive routes for insulin delivery, none of the novel non-invasive approaches have become part of established practice. In fact, until recently it was believed that as a result of limitations, non-invasive insulin was not a clinically realistic option. However, preliminary studies have indicated that inhaled insulin may emerge as an effective, well-tolerated, non-invasive alternative to subcutaneous regular insulin. The pharmacokinetics of inhaled insulin show a more physiological profile compared to conventional insulin; however, further studies to confirm long-term pulmonary safety and efficacy are needed.     

Effect of a novel tachykinin, substance K, on salivation in rats

A study of the effects of substance K (SK) and its synthetic fragments on salivation was performed. The rank order of potency of tachykinins that elicited salivation was as follows: physalaemin greater than substance P greater than eledoisin greater than kassinin greater than Arg-SK-(1-10) greater than SK-(1-10) greater than SK-(3-10). SK-(6-10) showed no activity. Atropine (1 mg/kg i.v.) had no effect on SK-induced salivation.     

Degludec: a novel basal insulin

Limitations of conventional human basal insulins like NPH have led to the development of more stable and peak less analogs. However, the first generation of basal analogs like glargine and detemir has certain shortcomings which do not allow them to be termed ideal basal insulins. Degludec, a novel basal insulin analog has the potential to overcome these limitations. This paper reviews the potential advantages of degludec over existing basal insulins and analogs. It discusses the basic and clinical studies performed on degludec so far, and highlights the possible role this molecule can play in the management of diabetes mellitus. In this paper, the recent patents on basal insulin have been reviewed so as to provide an insight into the advances in this field. In this article, we present a review of Degludec, as well as related patents.     

Glucose metabolism and insulin sensitivity in Dahl hypertensive rats.

There is increasing recognition that hypertension is only one facet of a metabolic syndrome that represents a cluster of risk factors including insulin resistance evident during long-term development of cardiovascular disease. The objectives of the present study were to evaluate glucose metabolism and insulin sensitivity in the Dahl genetic salt-sensitive rat model of hypertension and to find out whether there is a correlation between high blood pressure, salt sensitivity and insulin sensitivity. The experiments were performed in Wistar and Dahl salt-resistant (DSR) and salt-sensitive (DSS) rats given a normal or salt-loaded (2% NaCl in the drinking water) diet for 2 months. Glucose turnover, metabolic clearance of glucose and insulin sensitivity were determined using the euglycemic clamp technique in anesthetized animals. Four different concentrations of insulin were used (2.1, 4.2, 8.4 and 16.8 mg/kg/min) with results showing that there were no significant differences in serum glucose and insulin levels, glucose utilization and clearance and insulin sensitivity between Wistar and DSR; these groups remained normotensive throughout the 2-month experiment. However, DSS rats, even on a normal diet, developed hypertension by the end of the experiment and consistent with their hypertensive condition, significantly decreased glucose utilization and clearance and decreased insulin sensitivity were observed. The changes were more marked at higher insulin infusion rates (8.4 and 16.8 mg/kg/min). These results demonstrate that DSS rats with fully developed hypertension were insulin resistant. In contrast, DSR rats remained normotensive despite sodium loading. Sodium loading significantly exaggerated the hypertensive state of DSS rats but did not further increase insulin resistance. The results from respective weanling rats showed that even at this early stage before development of hypertension, DSS rats already had significantly increased serum insulin suggesting insulin resistance. In conclusion, the present results suggest that DSR genetically hypertensive rats were insulin resistant although insulin resistance was unrelated to high blood pressure or NaCl intake.     

An increase in tryptophan in brain may be a general mechanism for the effect of stress on sensitivity to pain

The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but not by valine and tryptophan (100 mg/kg, i.p.), was taken to indicate that an increase in the uptake of tryptophan in brain was involved in opioid-induced analgesia. Morphine-induced analgesia exhibited by rats that were habituated to the laboratory and not restrained did not involve an increase in the uptake of tryptophan in brain. However, a mild form of restraint, or exposure to a novel environment interacted with morphine to induce analgesia which involved an increase in the uptake of tryptophan in brain. These stressors did not affect sensitivity to pain in the absence of morphine. Analgesia induced by 3 hr of restraint, which was preventable by naltrexone (1 mg/kg, s.c.) but not reversible by naloxone (1 mg/kg, s.c.), also involved an increase in the uptake of tryptophan in brain. It is concluded that the endogenous opioid-induced analgesia that is induced by stress alone and analgesia induced by stress interacting with morphine, both depend on an increase in the uptake of tryptophan into the brain.     

Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1

The insulinotropic agent, exendin-4, is a long-acting analogue of glucagon-like peptide-1 (GLP-1) which improves glucose tolerance in humans and animals with diabetes, but the underlying mechanisms and the effects of exendin-4 on peripheral (muscle/fat) insulin action are unclear. Previous in vivo and clinical studies have been difficult to interpret because of complex, simultaneous changes in insulin and glucagon levels and possible effects on hepatic metabolism. Thus, the comparative effects of exendin-4 and GLP-1 on insulin-stimulated 2-[3H]deoxyglucose (2-DOG) uptake were measured in fully differentiated L6 myotubes and 3T3-adipocytes, including co-incubation with inhibitors of the PI-3-kinase (wortmannin) and mitogen-activated protein (MAP) kinase (PD098059) pathways. In L6 myotubes, there was a concentration-dependent and PI-3-kinase-dependent increase in insulin-stimulated 2-DOG uptake with exendin-4 and GLP-1, e.g. for exendin-4 the C(I-200) value (concentration of insulin required to increase 2-DOG uptake 2-fold) decreased from 1.3 +/- 1.4 x 10(-7)M (insulin alone, n=16) to 5.9 +/- 1.3 x 10(-8)M (insulin+exendin-4 0.1nM, n=18, P<0.03). A similar insulin-sensitizing effect was observed with exendin-4 in 3T3-adipocytes, but GLP-1 had no effect on adipocyte insulin sensitivity. In conclusion, this is the first direct evidence showing that exendin-4 increases insulin-stimulated glucose uptake in muscle and fat derived cells via a pathway that involves PI-3-kinase activation. Furthermore, the contrasting responses of exendin and GLP-1 in 3T3-adipocytes suggest that the peripheral insulin-sensitizing effect of exendin-4 (in contrast to the insulinotropic effect) does not involve the GLP-1 receptor pathway.     

Beneficial impact of Zingiber zerumbet on insulin sensitivity in fructose-fed rats

Zingiber zerumbet (L) Smith (Zingiberaceae), commonly known as the pinecone or shampoo ginger, is distributed in many parts of Asia. It has been demonstrated that the aqueous extract of Z. zerumbet exerted a potential blood glucose lowering effect in normoglycemic and streptozotocin-induced hyperglycemic rats. The present study was undertaken to clarify whether the ethanol extract of Zingiber zerumbet (EEZZ) is effective in improving insulin resistance. Insulin resistance was induced in rats by feeding a high-fructose diet for six weeks. Thereafter, rats were maintained on the same diet and treated with oral EEZZ or pioglitazone once daily for eight weeks. At the end of treatment, the degree of basal insulin resistance was measured by homeostasis model assessment (HOMA-IR). Insulin sensitivity was calculated using the composite whole body insulin sensitivity index (ISIcomp). Protein expression was evaluated by immunoblotting. Phytochemicals in EEZZ were determined through liquid chromatography-tandem mass. Not only curcumin but also quercetin and kaempferol were abundant in EEZZ. EEZZ (300 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing HOMA-IR and elevating ISIcomp as well as enhancing hepatic glycogen accumulation. Elevated glycosylated hemoglobin levels and hyperinsulinemia were ameliorated by EEZZ. Further, EEZZ enhanced the action of insulin on muscle glucose transporter subtype 4 translocation and attenuated hepatic phosphoenolpyruvate carboxykinase expression. This study suggests that EEZZ may be an ethnomedicine for improving insulin sensitivity.     

Renal response to infusion of dopamine precursors in anaesthetized rats

In the present study the renal response to intravenous infusion of the catecholamine precursors l-dihydroxyphenylalanine (l-DOPA) or l-tyrosine was investigated in thiopentone sodium-anaesthetized Sprague-Dawley rats. Glomerular filtration rate (GFR) was assessed by renal clearance of inulin, urinary concentration of dopamine (U_DAV) by HPLC and sodium excretion (U_NaV) by flame photometry. We found that basal U_DAV was 6.5 ± 0.5 pmol/min per 100 g body weight (mean ± SEM). Intravenous infusion of l-tyrosine at 0.1–3.0 μmol/min dose dependently enhanced U_DAV (17 ± 3 to 144 ± 14 pmol/ min respectively) with higher doses of l-tyrosine resulting in no further increase in U_DAV. Compared with l-tyrosine administration significantly lower doses of l-DOPA (0.07 to 35 nmol/min) caused increases in U_DAV which were orders of magnitude higher (18 ± 1 to 7800 ± 470 pmol/min, respectively) and did not show saturation characteristics. GFR did not change in response to l-tyrosine or l-DOPA infusion. No variations in urinary flow rate or in U_NaV could be observed which were significantly correlated to changes in U_DAV. In contrast, intravenous infusion of dopamine at a dose of 6 nmol/min significantly increased GFR by 35 ± 6.2% and urinary flow rate by over 2-fold. Immunohistochemistry with light microscopy revealed no tyrosine hydroxylase in the kidney. Therefore, dopamine synthesis in the tubular cells mainly depends on the renal supply of l-DOPA. The unchanged GFR and U_NaV in spite of large variations of U_DAV argue against the hypothesis that intratubular dopamine plays a functional role in the regulation of hemodynamics or sodium transport in the kidney. Renal dopamine excretion may rather represent an effective pathway for the elimination of catecholamine precursors from the plasma. Received: 5 February 1997 / Accepted: 24 July 1997     

Nitric oxide and prostacyclin pathways: an integrated mechanism that limits myocardial infarction progression in anaesthetized rats.

Nitric oxide (NO) and cyclooxygenase-derived prostaglandins, such as prostacyclin (PGI2), are involved in vascular homeostasis. To better understand the reciprocal role of both NO and PGI2 on myocardial infarction in the rat, we have investigated the cardioprotective effect of nitro-naproxen, isosorbide dinitrate (ISDN), L-arginine, defibrotide and naproxen. In this study, male Wistar rats were treated orally once a day for 5 consecutive days with the compounds under investigation and then, under anesthesia, the animals were subjected to acute myocardial ischemia (30 min) and reperfusion (120 min). Systemic blood pressure, left ventricular pressure and related parameters of cardiac mechanics were recorded. Ventricular arrhythmias and infarct size of the left ventricular wall were also evaluated. Furthermore, cardiac myeloperoxidase (MPO) and plasma creatine phosphokinase (CPK) activities were determined. Defibrotide, nitro-naproxen, ISDN and L-arginine all provided a cardioprotection characterized by significant prevention of arrhythmias with high survival rate of the rats. Infarct size restriction was paralleled by reduction of both cardiac MPO and plasma CK. Cardioprotection of nitro-naproxen, ISDN and L-arginine involve nitrites/nitrates and PGI2-increased in the circulation associated to a reduction of thromboxane B2 (TXB2) in the blood. Defibrotide displays a cardioprotection by increasing PGI2 release and by reducing TXB2 in the blood. Naproxen was devoid a lower protecting activity on myocardial infarction, and PGI2 inhibition may have played a critical role in this context. The results suggested that the increase of both NO and PGI2 brings about a cascade of integrated cellular and molecular events which are of paramount importance in prevention of myocardial ischemic insult.     

中药黄芪改善低剂量地塞米松处理大鼠胰岛素敏感性的分子基础

目的研究中药黄芪的多糖部分与皂苷部分对地塞米松诱导胰岛素抵抗大鼠的胰岛素敏感性的影响,探讨何者为黄芪改善作用的主要活性部位及其对胰岛素抵抗相关基因表达的影响。方法以2μg/天的剂量给雄性SD大鼠（每组6只）皮下注射地塞米松注射液,连续4周,同时给以相同生药剂量（10g生药/kg）的黄芪多糖提取物或黄芪皂苷提取物。试验结束后,动物处死取血,测定血清甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、血糖与胰岛素水平;取肾脏组织与睾丸脂肪垫提取总RNA,采用RT-PCR方法分别检测血管紧张素原（angiortensinogen）、脂联素（adiponectin）、瘦素（leptin）、肿瘤坏死因子（TNF-α）与甘油醛-3-磷酸脱氢酶（GAPDH）基因的表达水平。结果黄芪多糖提取物与黄芪皂苷提取物均表现出降低大鼠血清甘油三酯、血糖与胰岛素水平的作用,在同等生药剂量下,黄芪皂苷组对大鼠胰岛素敏感性指数的改善优于黄芪多糖组。两种提取物均能显著降低肾脏组织中血管紧张素原的表达及脂肪组织中肿瘤坏死因子α的表达,并同时上调脂联素与瘦素基因的表达,两种处理间未发现显著性差异。结论中药黄芪的多糖部分与皂苷部分均有增加胰岛素敏感性的作用,该作用可能与下调血管紧张素原、肿瘤坏死因子α基因及上调脂联素与瘦素基因的mRNA水平密切相关,部分说明了黄芪对II型糖尿病与糖尿病肾病的改善作用。两个提取部分未表现出作用上的显著性差异提示其中可能含有其他共性的重要活性成分有待发现。