Diabetes, inflamação e remédios chineses tradicionais.


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Diabetes, inflamação e remédios chineses tradicionais.

  1. 1. review article Diabetes, Obesity and Metabolism 13: 289–301, 2011. © 2011 Blackwell Publishing Ltd article reviewDiabetes is an inflammatory disease: evidence fromtraditional Chinese medicinesW. Xie1 & L. Du21 Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China2 Laboratory of Pharmaceutical Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing, ChinaDiabetes is usually associated with inflammation. Inflammation contributes to the development of diabetes. Traditional Chinese medicines(TCM) play an important role in lowering blood glucose and controlling inflammation. Many studies show that TCM with hypoglycaemiceffects, for example Radix Astragali, Radix Rehmanniae, Radix Trichosanthis, Panax Ginseng, Fructus Schisandrae, Radix Ophiopogonis, RhizomaAnemarrhenae, Radix Puerariae, Fructus Lycii, Poria, Rhizoma Coptidis, Rhizoma Dioscoreae, Rhizoma Polygonati, Radix Salviae Miltiorrhizae,Radix Glycyrrhizae, Semen Trigonellae, Momordica charantia, Allium sativum, Opuntia stricta, Aloe vera, Cortex Cinnamomi, Rhizoma CurcumaeLongae, and so on, have nearly independent anti-inflammatory action. Antihyperglycaemic compounds, for example berberine, puerarin,quercetin, ferulic acid, astragaloside IV, curcumin, epigallocatechin gallate, resveratrol, tetrandrine, glycyrrhizin, emodin and baicalin, used inTCM also have anti-inflammatory effects. These studies suggest that TCM might exert hypoglycaemic effects that are partly mediated by theanti-inflammatory mechanisms. However, small amounts of TCM with potent anti-inflammatory action does not have any hypoglycaemic effect.This indirectly indicates that diabetes may be a low-grade inflammatory disease and potent regulation of inflammatory mediators may not berequired. Studies of TCM add new evidences, which indicate that diabetes may be an inflammatory disease and slight or moderate inhibition ofinflammation might be useful to prevent the development of diabetes. Through this review, we aim to develop more perspectives to indicatethat diabetes may be an inflammatory disease and diverse TCM may share a common antidiabetic property: anti-inflammatory action. Furtherstudies should focus on and validate inflammation-regulating targets of TCM that may be involved in inhibiting the development of diabetes.Keywords: antidiabetic drug, diabetes, inflammation, traditional Chinese medicinesDate submitted 21 August 2010; date of first decision 23 September 2010; date of final acceptance 4 November 2010Introduction may contribute to their antidiabetic action. Conversely, it can be concluded that diabetes might be an inflammatory disease,Diabetes is a growing health problem across the world. It has although there is no solid evidence at the present time tobeen postulated that diabetes is a manifestation of an ongoing support this conclusion.chronic low-grade inflammation. Inflammation is defined as Chinese herbal formulas with antidiabetic effects are wella cascade of phenomena induced in response to different developed such that a number of these formulas havepathological stimuli and tissue injury. Chronic subclinical commonly been used in diabetic patients since ancientinflammation is associated with insulin resistance, a situation times. Li et al. systemically listed 86 natural medicines withof increased risk for developing diabetes [1]. Inflammatory regard to their origin, antidiabetic active principles and/orprocesses seem to play an important role in the development pharmacological test results in China [8]. Jia et al. haveof diabetes and its late complications [2]. reviewed antidiabetic herbal drugs officially approved in China The role of inflammation in the pathogenesis of type 2 and showcase eight antidiabetic herbal formulas [9]. Thesediabetes and its vascular complications was confirmed by authors believe that polysaccharide-containing herbs restoreinterventional studies. It has been shown that metformin, functions of pancreatic tissues and cause an increase in insulinperoxisome proliferator-activated receptor (PPAR)-γ agonist, output from the functional β cells, while other ingredientsglyburide and salicylates reduce the incidence of type 2 diabetes enhance microcirculation, increase the availability of insulinand its vascular complications partly via anti-inflammatory and facilitate metabolism in insulin-dependent processes. Liumechanisms [3–6]. It is also reported that insulin suppresses et al. have also conducted a systemic review of Chinese herbalfactors of inflammation in humans [7]. These studies indicate medicines for type 2 diabetes mellitus, and show that 69that anti-inflammatory effects of classic hypoglycaemic drugs different herbal medicines lower blood sugar, thereby relieving symptoms in patients with diabetes [10]. Qi et al. also report on the most frequently used 10 Chinese herbs in the periodCorrespondence to: Lijun Du, Laboratory of Pharmaceutical Sciences, School of LifeSciences, School of Medicine, Tsinghua University, Beijing 100084, China. from 2004 to 2009, for the treatment of diabetes and itsE-mail: lijundu@mail.tsinghua.edu.cn complications, that include Radix Astragali, Rhizoma Dioscoreae
  2. 2. review article DIABETES, OBESITY AND METABOLISM(RD), Radix Rehmanniae, Radix Salviae Miltiorrhizae, Radix TCM With Both Hypoglycaemic andPuerariae, Rhizoma Coptidis, Fructys Lycii, Poria, Rhizoma Anti-inflammatory ActivitiesAlismatis and Fructus Corni [11]. Wang and Wylie-Rosettselected 23 herbs and 5 herbal formulas in the treatment TCM are consisted of several herbal formulas, individual herbsof type 2 diabetes for review and indicated that the use of and active extracts or chemical components. We select the top 15 herbs most commonly prescribed in traditional ChineseChinese herbal medicines in diabetes is promising, although formulas in the treatment of type 2 diabetic patients and arethey are yet to be proven by further research [12]. approved by the State Food & Drugs Administrator (SFDA) However, it is unclear whether these hypoglycaemic Chinese in the mainland of China (unpublished data). These herbsherbs would have as potent anti-inflammatory properties as not only have antihyperglycaemic action but they also havethat of Western hypoglycaemic drugs. The Chinese herbs inves- anti-inflammatory effects (Table 1). In addition to these herbstigated are mostly qi-invigorating, heat-clearing and detoxify- from Chinese formulas, other individual hypoglycaemic herbsing drugs, as described previously in the theory of traditional also have anti-inflammatory effects. These anti-inflammatoryChinese medicines (TCM) [13]. Heat-clearing and detoxifying effects do not appear to be the result of hypoglycaemicdrugs usually have anti-inflammatory effects [14]. In particu- effects. These reported studies indicate that Chinese herbslar, the main active compounds, for example polysaccharides, exert a hypoglycaemic effect via their anti-inflammatoryterpenoids, flavonoids and alkaloids, in hypoglycaemic Chinese mechanism.herbs usually have wide pharmacological effects includinganti-inflammatory action. Therefore, it was not difficult to Traditional Chinese Medicinesspeculate that diverse hypoglycaemic TCM might all have Huang Qi (Radix Astragali). In theories of TCM, Radixanti-inflammatory effects. These effects might contribute their Astragali replenishes qi to invigorate yang, has beneficialbeneficial effects by inhibiting the development of diabetes effects on lungs to strengthen the body, promotes diuresisas diabetes is associated with an inflammatory process. In and relieves edema, cures skin infection and promotes tissuethis article, we systemically review anti-inflammatory evi- regeneration. Radix Astragali is the most widely used herbdences from TCM in the treatment of diabetes. This review in traditional Chinese formulas in the treatment of diabetes.aims to ascertain whether hypoglycaemic TCM share common Astragalus polysaccharides (APS) exerts a hypoglycaemic effectaction pathways in addition to their routine mechanisms of by decreasing the stress on the endoplasmic reticulum andaction and, further, to understand the inflammatory nature of then inhibiting the expression of protein tyrosine phosphatasediabetes. 1B (PTP1B) in type 2 diabetic rats that have been induced byTable 1. Antihyperglycaemic and anti-inflammatory effects of the top 15 most frequently prescribed herbs in 30 formulas and other individual herbprescriptions. Antihyperglycaemic Anti-inflammatoryNo. TCM activity (references) activity (references) Active components 1 Huang Qi (Radix Astragali) + [15–17] + [18,19] Polysaccharides 2 Di Huang (Radix Rehmanniae) + [20–22] + [23,24] Catalpol, oligosaccharide 3 Tian Hua Fen (Radix Trichosanthis) + [25] + [26] Glycans, trichosanthin 4 Ren Shen (Radix Ginseng) + [27–29] + [30,31] Saponins 5 Wu Wei Zi (Fructus Schisandrae) + [32,33] + [34] Lignans, polysaccharides 6 Mai Dong (Radix Ophiopogonis) + [35] + [36] Sapogenin 7 Zhi Mu (Rhizoma Anemarrhenae) + [37] + [38] Mangiferin 8 Ge Gen (Radix Puerariae) + [39,40] + [41] Puerarin (flavonoids) 9 Gou Qi (Fructus Lycii) + [42] + [43] Polysaccharides10 Fu Ling (Poria) + [44,45] + [46] Triterpene acid11 Huang Lian (Rhizoma Coptidis) + [47–49] + [50] Berberine12 Shan Yao (Rhizoma Dioscoreae) + [51] + [52,53] Saponins13 Huang Jing (Rhizoma Polygonati) + [54,55] + [56] Flavonoids, polysaccharides14 Dan Shen (Radix Salviae Miltiorrhizae) + [57] + [58,59] Tanshinone IIA (lignans)15 Gan Cao (Radix Glycyrrhizae) + [60,61] + [62] Glycyrrhetinic acidI Semen Trigonellae + [63] + [64,65] Diosgenin (saponin)II Momordica charantia + [66–70] + [71] Polypeptide-p, SaponinsIII Allium sativum + [72,73] + [74,75] Volatile oils, sulphur compoundsIV Cactus (Opuntia stricta) + [76] + [77] Polysaccharides, β-SitosterolV Aloe vera + [78] + [79] Aloe vera gelVI Rou Gui (Cortex Cinnamomi) + [80–83] + [84] Cinnamon oilVII Jiang Huang (Rhizoma Curcumae Longae) + [85,86] + [87] Curcuminoids and sesquiterpenoidsThe ‘+’ indicates that the compound has that particular activity.290 Xie and Du Volume 13 No. 4 April 2011
  3. 3. DIABETES, OBESITY AND METABOLISM review articlehigh-fat diets and low-dose streptozotocin (STZ) [15]. APS also Ren Shen (Radix Ginseng). In TCM, Ginseng is claimed toincreases glucose metabolism by increasing liver glycogenesis invigorate renal qi, strengthen qi of the spleen and lung,and skeletal muscle glucose translocation through activating promote production of the body fluids to quench thirst andAMP kinase (AMPK) in the same type of diabetic rats [16]. APS calm the mind to promote intelligence. Ginseng has beenimproves insulin sensitivity and exerts a hypoglycaemic effect reported effective, in many ancient Chinese medical literatures,in KK-Ay mice by regulating protein kinase B (PKB)/glucose to treat emaciation and symptoms such as thirst [27]. Ginsengtransporter (GLUT)4 signalling in skeletal muscle [17]. APS therapy significantly reduces fasting blood glucose (FBG)may be effective in the attenuation of insulitis and prevents β and homeostatic model assessment of insulin resistance incells from undergoing apoptosis in type 1 diabetic mice [18]. type 2 diabetic subjects compared with placebo [28]. GinsengRadix Astragali exhibits anti-inflammatory effects in Zymosan reduces hyperglycaemia in the diabetic mouse model, inducedair-pouch mice by inhibiting the expression of inducible by STZ [29]. However, ginseng has no effect on glucosenitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), regulation during acute or chronic administration in healthyinterleukin-6 (IL-6), interleukin-1β (IL-1β) and tumour volunteers [88]. Its effects include increased insulin secretion,necrosis factor (TNF)-α while also reducing the production of prevention of β-cell apoptosis, enhanced insulin sensitivitynitric oxide (NO) [19]. Its anti-inflammatory effect is attributed and promotion of thermogenesis [27]. Commonly, the activeto the inactivation of p38 and extracellularly regulated kinase1/2 components of ginseng are considered to be ginsenosides.(ERK1/2) and the inhibition of nuclear factor-κB (NF-κB)- Ginsenoside Re inhibits intracellular inflammatory moleculesmediated transcription. including c-Jun N-terminal kinase (JNK) and NF-κB and enhances insulin sensitivity in 3T3-L1 adipocytes and high-fatDi Huang (Radix Rehmanniae). In theories of TCM, Radix diet rats [30]. Ginsenoside Ro inhibits vascular permeabilityRehmanniae (RR) is used to clear away heat and cool the in mice that have been induced by acetic acid and reducesblood, nourish yin and promote the production of the body acute paw edema in rats induced by the compound 48/80 orfluids. RR has a very long history of use in TCM and is carrageenan [31].usually one of the principal herbs in many herbal formulasused in the treatment of diabetes. RR has been reported to Wu Wei Zi (Fructus Schisandrae). Fructus Schisandrae, incontain more than 70 compounds and has a broad range of TCM, is used as an astringent of the lung to treat coughpharmacological effects [20]. Catalpol, with its hypoglycaemic and asthma, nourish the kidney, promote the production ofeffects, is one of the most important compounds in RR [21]. body fluid and inhibit perspiration, condense the essence andNext, oligosaccharides exert a significant hypoglycaemic effect stop diarrhoea, nourish the heart and calm the mind. Fructusin normal and alloxan-induced diabetic rats [22]. The mecha- Schisandrae lowers blood glucose and improves insulin resis-nism of RR for regulating glucose metabolism has a correlation tance in 90% pancreatectomized diabetic rats maintained onwith the regulation of the neuroendocrine system, stimulates high-fat diets and may have been mediated by the mechanismthe secretion of insulin, improves insulin resistance, enhances of increased insulin sensitivity [32]. Dibenzocyclooctadieneactivity of liver glucokinase and glucose-6-phosphate dehy- lignans, the active principle isolated from Fructus Schisan-drogenase, decreases hepatic glycogen content and stimulates drae, reduces the level of blood glucose by stimulating glucoseglucose uptake [20]. Treatment with RR brings about decreased uptake into peripheral tissues [33]. Schisandrin is the mainplasma C-reactive protein (CRP) levels compared with diabetic active ingredient isolated from the fruit of Schisandra chinensiscontrols [23]. RR injections inhibit increase in total white blood Baill. Schisandrin significantly inhibits carrageenan-inducedcell and neutrophil counts and attenuate the increase in TNF-α, paw edema and acetic acid-induced vascular permeability inO2− , myeloperoxidase induced by lipopolysaccharides (LPS), mice. Further, schisandrin has a protective effect on LPS-and minimize pathophysiologic changes including neutrophil induced sepsis [34]. Schisandrin also inhibits the production ofinfiltration and mucosal edema in the tracheae in a rat model NO and prostaglandin E2 (PGE2), and attenuates the expres-of lung inflammation, induced by LPS [24]. sion of COX-2 and iNOS, which may be mediated by the inhibition of NF-κB, JNK and p38 mitogen-activated proteinTian Hua Fen (Radix Trichosanthis). In the theory of TCM, kinase (MAPK) activities in RAW 264.7 macrophage cells.Radix Trichosanthis has actions such as clearing of heat, pro-motion of production of body fluids, resolution of swelling Mai Dong (Radix Ophiopogonis). Radix Ophiopogonis (RO),and drainage of pus. This herb is used in the treatment of another top herb used in TCM, nourishes yin and increases lungdiabetes and increased thirst. The water extract of the roots secretions, benefits the stomach and regenerates body fluids,of Trichosanthes kirilowii is found to reduce plasma glucose clears away heart-heat and relieves anxiety. Intraperitoneallevels in mice [25]. Five glycans, called trichosans A, B, C, administration of the n-butanol extract of RO decreases bloodD and E, have been isolated from the water extract of the glucose levels in normal and STZ-induced diabetic mice [35].roots of Trichosanthes kirilowii, and have manifested hypogly- RO also tends to suppress epinephrine-induced hyperglycaemiacaemic effects in normal mice. The main glycan, trichosan A, in mice. Aqueous extract from RO significantly inhibits xylene-also exhibits activity in alloxan-induced diabetic mice. Tri- induced ear swelling and carrageenan-induced paw edema inchosanthes inhibits TNF-α and IL-1β production in peripheral mice following oral administration [36]. RO also remarkablyblood mononuclear cells stimulated by LPS, indicating definite suppresses carrageenan-induced pleural leucocyte migrationanti-inflammatory activity [26]. in rats and Zymosan A-evoked peritoneal total leucocyte andVolume 13 No. 4 April 2011 doi:10.1111/j.1463-1326.2010.01336.x 291
  4. 4. review article DIABETES, OBESITY AND METABOLISMneutrophil migration in mice. Ruscogenin and ophiopogonin Fu Ling (Poria). In TCM, Poria is utilized to promoteD are two of the active components of this herb. diuresis to resolve dampness from the lower energizer, invigorate the spleen and tranquilize the mind. Poria extract,Zhi Mu (Rhizoma Anemarrhenae). In TCM, Rhizoma Anemar- and triterpenes therein, lowers postprandial blood glucoserhenae (RA) is used to clear away heat and purge fire, nourish levels in db/db mice via enhanced insulin sensitivity [44].yin and aid moisturization. The aqueous extract of RA reduces The triterpene acid compound dehydrotrametenolic acid,blood glucose levels following oral administration and also isolated from Poria, can reduce hyperglycaemia in db/dbtends to reduce serum insulin levels in KK-Ay mice [37]. RA- mice and act as an insulin sensitizer [45]. Poria extract istreated KK-Ay mice have shown significantly lowered blood effective in mitigating inflammation in different in vivo modelsglucose levels in an insulin tolerance test. The antidiabetic of inflammation induced by 12-O-tetradecanoyl-phorbol-13-action of RA may be due to decreased insulin resistance. Fur- acetate, ethyl phenylpropiolate and phospholipase A2 [46].ther, mangiferin and its glucoside have been confirmed as active Active components in this herb are lanostane triterpenes.components of RA. It is reported that the total polysaccharideextracts from RA may inhibit inflammatory responses in var- Huang Lian (Rhizoma Coptidis). In TCM, Rhizoma Coptidisious models [38]. Timosaponin B-II, derived from a purified is used to clear away heat and remove dampness, purge theextract of RA, significantly inhibits the increase in IL-1β, TNF- sthenic fire and eliminate toxic materials. Rhizoma Coptidisα and IL-6, on both mRNA and protein levels from BV2 cells has been used to treat diabetes for more than 1400 yearsstimulated by LPS in a dose-dependent manner. in China. Berberine is one of the main active alkaloids present in Rhizoma Coptidis. Berberine reduces weight gain,Ge Gen (Radix Puerariae). In TCM, Radix Puerariae is used enhances insulin sensitivity and decreases blood glucose into expel pathogenic factors in the muscles to abate heat, both dietary and genetic animal models of type 2 diabetes [47].expel skin eruptions, promote the production of body fluid to Berberine activates AMPK via the inhibition of mitochondriadecrease thirst, uplift yang and to relieve diarrhoea. Intravenous function [48]. Berberine has protective effects on β cells ininjection of puerarin, purified from Radix Puerariae, decreases STZ- and high-carbohydrate/high-fat diet-induced diabeticplasma glucose levels in a dose-dependent manner in STZ- rats [47]. Berberine reduces glucose absorption in the intestineinduced diabetic rats [39]. Radix Puerariae increases glucose by inhibiting intestinal disaccharidases [49]. Rhizoma Coptidisutilization in diabetic rats with insulin deficiency. Moreover, is well known for its anti-inflammatory activity. Incubationthe mRNA and protein levels of GLUT4 in soleus muscle with Rhizoma Coptidis and berberine strongly inhibitedare increased after intravenous administration of puerarin LPS-induced monocyte chemoattractant protein (MCP)-1in STZ-induced diabetic rats. Puerarin may activate α1- production in RAW 264.7 cells [50]. The increase in theadrenoceptors in the adrenal gland to enhance the secretion of transcription factors activator protein-1 (AP-1) and NF-κB isβ-endorphin, with resultant reduction in plasma glucose levels inhibited by Rhizoma Coptidis in a dose- and time-dependentin STZ-induced diabetic rats. Puerarin can protect islets against manner.oxidative stress induced by H2 O2 probably by its mechanism Shan Yao (Rhizoma Dioscoreae). In TCM, RD invigoratesof action increasing catalase and superoxide dismutase the spleen and stomach, promotes production of the bodyactivities [40]. Puerarin also acts as an anti-inflammatory agent. fluids and benefits lungs, invigorates kidneys and preservesPuerarin inhibits the expression of the protein and mRNA the essence. RD is a common food ingredient in China. RDlevels of CRP in LPS-induced peripheral blood mononuclear improves fructose-induced decrease in the insulin-stimulatedcells [41]. The inhibition of CRP expression is due to a dose- glucose disposal rate after 3 days of treatment [51]. In addition,dependent inhibition of phosphorylation and degradation of oral administration of RD into STZ-induced diabetic ratsinhibitor-κB (I-κB), which results in a reduction of p65 NF-κB for 10 days increases sensitivity to exogenous insulin. RDnuclear translocation. significantly inhibited TNF-α and IL-1β production and downregulated COX-2 and iNOS expression in humanGou Qi (Fructus Lycii). In TCM, Fructus Lycii (FL) is claimed to fibroblast-like synovial cells that were stimulated by IL-1β andtone the kidney and benefit essence, while nourishing the liver TNF-α. Further, RD effectively reduced the level of reactiveand improving eyesight. Polysaccharides extracted following oxygen species (ROS) in these cells [52]. The extract of RD hastreatment of FL for 28 days bring about a significant decrease been shown to decrease damage in renal tubules, inflammationin concentrations of FBG, total cholesterol and triglycerides in the central vein and necrosis in the liver tissue of rats [53].(TG) in alloxan-induced diabetic mice [42]. Further, FLpolysaccharides significantly increase body weight in this Huang Jing (Rhizoma Polygonati). In TCM, Rhizoma Polygo-animal model. FL polysaccharides are effective in the protection nati (RP) is used to increase secretions in the lung, nourish andof liver and kidney tissue from damage as shown in STZ- invigorate the kidney and benefit qi. Intraperitoneal admin-induced diabetic rat; this implies that FL polysaccharides may istration of the methanol extract of RP lowers blood glucosebe of use as antihyperglycaemic agents. FL polysaccharides have levels in normal and STZ-induced diabetic mice [54]. How-been identified as one of the active ingredients responsible for ever, the hypoglycaemic effects are not accompanied by anyFL’s biological properties. FL polysaccharides can attenuate the alteration in serum insulin in these mice. RP decreased hepaticinflammatory reaction in endothelial cells and this is mediated glucose output and exerted a hypoglycaemic effect, presumablyby inhibition of the CRP and NO production [43]. because of the reduction of GLUT2 expression in the total292 Xie and Du Volume 13 No. 4 April 2011
  5. 5. DIABETES, OBESITY AND METABOLISM review articlemembrane of the liver [55]. One of the active components of aglycone of saponins, in fenugreek has been identified toRP is identified as a spirostanol glycoside. In addition, pharma- promote adipocyte differentiation and to inhibit expressions ofcological research indicates that Polygonatum polysaccharidi several molecular candidates associated with inflammationhas anti-inflammatory effects [56]. in 3T3-L1 cells. Diosgenin has been shown to suppress inflammation mediated by its inhibition of TNF-induced NF-Dan Shen (Radix Salviae Miltiorrhizae). In TCM, Radix Salviae κB activation in tumour cells [65].Miltiorrhizae promotes blood circulation to remove bloodstasis, regulates menstruation to relieve pain, cools the blood Momordica Charantia. Momordica charantia (bitter melon) isto relieve carbuncle and clears away heat from the body a popular fruit used for the treatment of diabetes and relatedand tranquilizes the mind. Tanshinone IIA, an important conditions amongst the indigenous populations of Asia, Southcomponent extracted from Salvia miltiorrhiza, can improve America, India and East Africa. Many animal and humanglucose tolerance and inhibits adipogenesis in rats fed on a high- studies have proved the potential role of Momordica charantiafat diet, and might be beneficial in the treatment of diabetic in glycaemic control [66]. Momordica charantia reduces bloodpatients with complex metabolic disorders [57]. Tanshinone glucose levels and also significantly lowers the serum insulinIIA has protective effects on several pharmacological targets levels in KK-Ay mice after 3 weeks of oral administration [67].in the progression of diabetic nephropathy [89]. Tanshinone The hypoglycaemic mechanisms are related to its inhibitionIIA restores impaired neural functions in the experimental of PTP1B [68], activation of AMPK [69], increase in GLUT4diabetic rats [90] and also protects the myocardium against protein content in the plasma membrane [67] and promotionischaemia/reperfusion injury [91]. Danshen is used to treat of the recovery of β cells [92]. Major active compounds inacute pancreatitis and its mechanisms of action include this herb include cucurbitane triterpenoids [93], polypeptide-improvement of microcirculatory disturbances, elimination p [70], saponins, and so on. The butanol soluble fraction ofof oxygen free radicals, modulation of the metabolism of lipid bitter gourd placenta extract strongly suppresses LPS-inducedinflammatory mediator and blocking of calcium inflow with TNF-α production and expression of various LPS-inducedsubsequent prevention of calcium overload [58]. Tanshinone inflammatory genes in RAW 264.7 cells [71]. The butanolIIA exerts anti-inflammatory effects mediated by inhibition of fraction significantly suppresses NF-κB DNA-binding activityiNOS gene expression and NO production, as well as inhibition and phosphorylation of p38, JNK and ERK MAPKs.of inflammatory cytokine (IL-1β, IL-6 and TNF-α) expression Allium Sativum. Garlic (Allium sativum), which is a com-via the endoplasmic reticulum-dependent pathway in LPS- mon cooking spice and has a long history of use as ainduced RAW 264.7 cells [59]. folk remedy, has been reported to have antidiabetic activity. Antioxidant, anti-inflammatory and antiglycative propertiesGan Cao (Radix Glycyrrhizae). In TCM, Radix Glycyrrhizae of garlic play an important role in preventing progres-functions by enriching qi and invigorating the stomach and sion of diabetes and the development of diabetes-relatedspleen, moistening the lung and clearing away phlegm, clearing complications [72]. Both garlic oil and diallyl trisulphideaway heat and toxins and relieving spasm and alleviating improve glycaemic control in STZ-induced diabetic ratspain. Roasted Glycyrrhizae Radix, containing glycyrrhetinic acid through increased insulin secretion and sensitivity [73]. Sul-(GA), improves glucose tolerance better than raw Glycyrrhizae phur compounds isolated from garlic exert anti-inflammatoryRadix extract by enhancing insulinotropic action in partially properties. S-Allyl-l-cysteine sulphoxide can control TNF-pancreatectomized diabetic mice [60]. Glycyrin, one of the α-mediated inflammation and mediate vascular disease [74].main PPAR-γ ligands of licorice, significantly lowers the blood Thiacremonone, another novel sulphur compound from gar-glucose level [61]. GA inhibits TNF-α-stimulated intercellular lic, suppresses 12-O-tetradecanoylphorbol-13-acetate-inducedadhesion molecule-1 (ICAM-1) expression, leading to a (1 μg/ear) ear edema [75]. Thiacremonone (1–10 mg/kg)decrease in monocytes adhering to human umbilical vein administered directly onto the plantar surface of hind pawendothelial cells [62]. This inhibition is attributed to GA also suppresses carrageenan (1.5 mg/paw) and Mycobacteriuminterruption of both JNK/c-Jun and I-κB/NF-κB signalling butyricum (2 mg/paw)-induced inflammatory and arthriticpathways, which decrease AP-1 and NF-κB-mediated ICAM-1 responses, which may be related to the inhibition of expressionexpressions. The results imply that GA may manifest anti- of iNOS and COX-2.inflammatory effects. Opuntia Stricta. Opuntia stricta (cactus) has an effect onSemen Trigonellae. Oral administration of Semen Trigonellae lowering blood glucose levels in patients with type 2 diabetes(fenugreek) seeds soaked in hot water significantly decreased mellitus. Blood glucose and glycated haemoglobin (HbA1c)FBG levels in patients with type 2 diabetes mellitus [63]. levels are reduced to normal values by a combined treatment of4-Hydroxyisoleucine, an unusual amino acid isolated from insulin and Opuntia extract in STZ-induced diabetic rats [76].fenugreek seeds, when administered orally in mice significantly When insulin is withdrawn from this combined therapy,inhibits elevation of blood glucose and plasma insulin levels in Opuntia stricta extract alone can maintain normoglycaemicdb/db diabetic mice, which is evidenced by the enhancement state in diabetic rats. Rats receiving combination treatment ofof insulin sensitivity and glucose uptake in peripheral insulin and Opuntia extract for 7 weeks followed by Opuntiatissues. Fenugreek also inhibits macrophage infiltration into extract alone have shown rapid return of blood glucoseadipose tissues and decreases the mRNA expression levels levels than those of non-diabetic rats after being challengedof inflammatory genes [64]. In addition, diosgenin, a major with exogenous glucose administration. Polysaccharides mayVolume 13 No. 4 April 2011 doi:10.1111/j.1463-1326.2010.01336.x 293
  6. 6. review article DIABETES, OBESITY AND METABOLISMbe responsible for this hypoglycaemic activity. The ethanol pathway [86]. A turmeric preparation depleted of essential oilsextract of Opuntia stricta manifests potent anti-inflammatory profoundly inhibits joint inflammation and periarticular jointaction [77]. In adjuvant-induced chronic inflammation model destruction in a dose-dependent manner. In vivo treatmentin mice, the active anti-inflammatory principle has been prevents local activation of NF-κB and the subsequent expres-isolated and identified as β-sitosterol. sion of NF-κB-regulated genes that mediate joint inflammation and destruction, including chemokines, COX-2 and receptorAloe Vera. Oral administration of processed Aloe vera gel activator of NF-κB ligand [87]. Further, inflammatory cell(PAG) for 8 weeks reduces blood glucose concentrations to influx, levels of PGE2 within a joint and periarticular osteoclasta normal level in these diet-induced obese mice [78]. In formation are inhibited by treatment with turmeric extract.addition, PAG significantly decreases plasma insulin. Theantidiabetic effects of PAG are also confirmed by intraperitonealglucose tolerance testing. PAG appears to lower blood glucose Compounds Derived From TCMconcentrations by decreasing insulin resistance. Phytosterols Active components of TCM mainly contain polysaccharides,derived from Aloe vera gel may act as active compounds in this flavonoids, terpenoids, alkaloids and so on. It is hypothesizedaction [94]. However, Aloe vera used topically, administered that these common chemical components might share similarintraperitoneally or by a combination delivery modulates mechanisms of action within different herbs. In addition toinflammatory responses [79]. The maximal effect is observed the well-defined berberine and puerarin described above, somewith the combined delivery, indicating modulation at local as other active components from Chinese herbal medicines arewell as systemic levels. This modulation could result from the found to have significant or moderate hypoglycaemic effects aspotential of Aloe vera to attenuate peroxidative damage by a well as anti-inflammatory action (figure 1).decrease in the levels of TNF-α, IL-1 and IL-6, and an increasein the level of superoxide dismutase. Quercetin. Quercetin, a bioflavonoid widely used in TCM, is a food component that may ameliorate diabetic symp-Rou Gui (Cortex Cinnamomi). In TCM, Cortex Cinnamomi toms. Diets containing 0.1 or 0.5% quercetin lowered thefunctions by supplementing fire and strengthening yang, STZ-induced increase in blood glucose levels and enhancedexpelling cold and alleviating pain and warming channels plasma insulin levels [95]. Dietary quercetin may improveto promote blood circulation. Intake of 2 g of cinnamon hepatic and pancreatic functions by facilitating cell prolif-for 12 weeks significantly reduces the HbA1c among patients eration through inhibition of Cdkn1a expression. Quercetinwith poorly controlled type 2 diabetes [80]. Cinnamon oil promotes glucose- and glibenclamide-induced insulin secre-(CO), when administered for 35 days, significantly decreases tion and protects β cells against oxidative damage through theFBG levels in an animal model of type 2 diabetes (KK- ERK1/2 pathway [96]. Quercetin enhances glucose metabolismAy mice) [81]. Meanwhile, glucose tolerance is improved, through activation of both silent mating type information reg-and the immunoreactive capacity of pancreatic islets β cells ulation 2 homolog 1 (SIRT1) and AMPK in HepG2 cells [97].is enhanced. Indeed, it is evident that Cortex cinnamomi Quercetin affects inflammation by modulating several intra-extract prevents STZ- and cytokine-induced β-cell damage cellular signalling kinases, phosphatases, enzymes and mem-by inhibition of NF-κB [82]. Further, cinnamon extracts brane proteins that are often crucial for a specific cellularincrease GLUT1 mRNA and decrease the expression of further function [98]. Quercetin attenuates lethal systemic inflamma-genes encoding insulin signalling pathway proteins [83]. The tion caused by endotoxaemia [99]. In macrophage cultures,main component of CO is cinnamaldehyde. Twig essential quercetin limits the activation of MAPK and NF-κB.oil and its major constituents such as trans-cinnamaldehyde,caryophyllene oxide, l-borneol, l-bornyl acetate, eugenol, β- Ferulic Acid. Ferulic acid (FA), a phenolic compound, is acaryophyllene, E-nerolidol and cinnamyl acetate significantly strong membrane antioxidant and is reported to have positiveinhibit NO and PGE2 production in LPS-activated RAW 264.7 effects on human health. FA at 0.01 and 0.1% of t basal dietcells [84]. significantly suppresses blood glucose levels in STZ-induced diabetic mice [100]. In KK-Ay mice, 0.05% FA suppressesJiang Huang (Rhizoma Curcumae Longae). In TCM, Rhi- blood glucose levels effectively. FA also stimulates insulinzoma Curcumae Longae is traditionally used to promote secretion from pancreatic β cells [101], protects against cellularcirculation of blood and qi, dredge the meridian passage to redox disruption and several oxidative stress-related diseases,alleviate pain. The ethanol extract of turmeric significantly including inflammation in animal studies [102], suppressesinhibits increase in blood glucose levels in type 2 diabetic NF-κB activation and modulates the expression of NF-KK-Ay mice [85]. In an in vitro evaluation, the extract stim- κB-induced, proinflammatory COX-2, iNOS, vascular cellulated human adipocyte differentiation in a dose-dependent adhesion molecule-1 (VCAM-1) and ICAM-1 [102]. Further,manner and showed human PPAR-γ ligand-binding activ- FA prevents the induction of ICAM-1 and VCAM-1 expressionity. The main constituents of the extract are identified as in a concentration-dependent manner after being stimulatedcurcumin, demethoxycurcumin, bisdemethoxycurcumin and by radiation [103]. The inhibitory effect of FA on adhesionar-turmerone, and it also has PPAR-γ ligand-binding activity. molecule expression is mediated by blockade of JNK.Curcumin increased GLUT4 expression and glucose uptakeinto skeletal muscle, isolated from Wistar rats, through the Astragaloside IV. Astragaloside IV, a new cycloartane-typephospholipase C (PLC)–phosphoinositide 3 kinase (PI3K) triterpene glycoside extract of Radix Astragalus membranaceus294 Xie and Du Volume 13 No. 4 April 2011
  7. 7. DIABETES, OBESITY AND METABOLISM review articleFigure 1. Antihyperglycaemic and anti-inflammatory compounds from traditional Chinese medicines (TCM) (structures were sourced fromhttp://www.pubchem.ncbi.nlm.nih.gov/).Bunge, at doses of 25 and 50 mg/kg, significantly decreases AS-IV improved TNF-α-induced insulin resistance in 3T3-L1blood glucose, TG and insulin levels, and inhibits mRNA and adipocytes [105]. AS-IV has been reported to have anti-protein expression as well as enzymatic activity of glycogen inflammatory effects in vivo [106]. AS-IV inhibits cytokine-phosphorylase (GP) and glucose-6-phosphatase (G-6-Pase) in and LPS-stimulated expression of adhesion molecules in, anddiabetic mice, induced by a high-fat diet and STZ [104]. The leucocyte adhesion to, endothelial cells. AS-IV’s inhibitionhypoglycaemic effect of this compound may be explained, in of the NF-κB pathway might be one underlying mechanismpart, by its inhibition of hepatic GP and G-6-Pase activities. contributing to its anti-inflammatory potential in vivo.Volume 13 No. 4 April 2011 doi:10.1111/j.1463-1326.2010.01336.x 295
  8. 8. review article DIABETES, OBESITY AND METABOLISMCurcumin. Curcumin, an antioxidant compound, lowers Glycyrrhizin. Glycyrrhizin treatment significantly lowers bloodblood glucose levels and ameliorates the long-term com- insulin level in diabetic KK-Ay mice [124]. The mice fedplications of diabetes in animal models of diabetes [107]. on a glycyrrhizin diet also have improved tolerance to oralCurcumin increases the phosphorylation of AMPK and its glucose loading 9 weeks after the beginning of test feeding.downstream target acetyl-CoA carboxylase (ACC) in cells with Glycyrrhizin inhibits the LPS/d-galactosamine-induced hepatic400 times the potency of metformin. Curcumin suppresses injury through prevention of inflammatory responses and IL-18hepatic gluconeogenesis. Curcumin inhibits proinflammatory production [125]. Further, it appears that glycyrrhizin preventscytokine concentrations in the serum and pancreas of STZ- IL-18-mediated inflammation in hepatic injury.treated animals [108]. Curcumin, in combination with aspirinor rofecoxib, causes a further decrease in serum TNF-α lev- Emodin. Emodin, a natural product and active ingredient ofels that could possibly be mediated by inhibition of the various Chinese herbs, significantly decreases blood glucoseCOX enzyme [109]. Curcumin attenuates the development levels in high-fat diet-fed- and low-dose STZ-induced diabeticof allergic airway inflammation and hyper-responsivity, pos- mice [126]. The glucose tolerance and insulin sensitivitysibly through inhibition of NF-κB activation in the asthmatic in the emodin-treated group were significantly improvedlung tissue [110]. compared with the controls. The activation of PPAR-γ and the modulation of metabolism-related genes likely mediate theEpigallocatechin Gallate. Epigallocatechin gallate (EGCG) is antidiabetic effects of emodin. Further, emodin is consideredone of the main compounds derived from green tea. EGCG can a potent and selective inhibitor of 11β-hydroxysteroidprevent abnormal changes in blood glucose and lipid profile and dehydrogenase type 1 [127]. Emodin can inhibit the activationattenuate hepatic lipid peroxidation in STZ-induced diabetic of NF-κB and the expression of ICAM-1 induced by LPSrats [111]. EGCGs have protective effect on the insulinoma-1 in corneas, protect against acute corneal injury and improve(INS-1) beta cells against oxidative stress both through antiox- symptoms in rats [128].idant effect and antiapoptotic signalling [112]. EGCG inhibits Baicalin. Baicalin, a flavonoid known for its radical scavengingERK and activates AMPK [113]. Pretreatment with EGCG sup- activity, significantly decreases plasma glucose levels in a dose-presses the secretion of monocyte chemoattractant protein-1 dependent manner in nicotinamide–STZ-induced diabeticand the activation of AP-1 in porcine aortic endothelial cells rat [129]. Administration of baicalin results in a significantstimulated by TNF-α [114]. EGCG attenuates LPS-induced increase in hepatic glycogen content and glycolysis, and alung injury by inhibition of the macrophage inflammatory reduction in serum TNF-α level. Baicalin significantly alleviatedprotein-2 and TNF-α production, as well as ERK1/2 and JNK the morphological injury to the pancreas caused by STZ.activation in macrophages stimulated by LPS [115]. Baicalin inhibits macrophage activation and protects mice fromResveratrol. Resveratrol, a polyphenolic SIRT1 activator, macrophage-mediated endotoxic shock. It also suppresses theshowed a significant antihyperglycaemic effect in type 2 diabetic increased generation of NO and expression of iNOS inducedob/ob mice [116]. The STZ–nicotinamide-induced diabetic by LPS or interferon-γ without directly affecting iNOS activityrats, when orally treated with resveratrol, exhibit significant in RAW264.7 cells and peritoneal macrophages [130].decrease in the levels of blood glucose and glycosylatedhaemoglobin [117]. Its antidiabetic properties may be mediated TCM With Anti-inflammatory Effects Onlyby enhanced insulin secretion and antioxidant competence inpancreatic β cells of diabetic rats [118]. Further, resveratrol However, many of the classic or potent anti-inflammatoryactivates APMK and increases energy metabolism. Resveratrol components in herbs, for example daphnetin [131], sinome-significantly inhibits airway inflammation in respiratory nine [132], tripterysium glucosides [133], decanoylacetalde-disease [119]. Resveratrol treatment decreases the expression of hyde [134], oxymatrine [135], phthalide lactones [136] andp65 and I-κB−α and ameliorates elevation in levels of TNF-α, tetramethylpyrazine [137] have no reported hypoglycaemicIL-6 and COX-2 in treated rats [120]. activities. Frequently used anti-inflammatory drugs are clas- sified as: non-steroidal anti-inflammatory and steroidalTetrandrine. Tetrandrine, an active plant alkaloid derived anti-inflammatory drugs. Non-steroidal anti-inflammatoryfrom Stephaniae tetrandrae, significantly decreases the plasma drugs include salicylates, acetaminophen, phenylbutazone,glucose levels in a dose-dependent manner in STZ-induced indomethacin, ibuprofen, colchicines, and so on. With thediabetic rats [121]. Tetrandrine prevents the spontaneous exception of salicylates [138,139], these drugs have no antidi-development of diabetes mellitus in biobreeding (BB) abetic effects. Of note, most patients requiring non-steroidalrats [122]. Tetrandrine has the ability to enhance glucose anti-inflammatory drugs for pain control show a high inci-utilization in peripheral tissue and protect islet β cells from dence of gastrointestinal and cardiovascular risk factors [140].injury induced by alloxan. Tetrandrine, remarkably, suppresses Steroidal anti-inflammatory drugs increase blood glucose lev-the LPS induction of NO release and PGE2 generation [123]. els, for example dexamethasone [141]. Therefore, it may beIt also significantly attenuates LPS-induced transcription of inappropriate to use potent anti-inflammatory drugs to pre-proinflammatory cytokines (TNF-α, IL-4 and IL-8) in a dose- vent the development of diabetes. In turn, these results indicatedependent manner. Further, tetrandrine significantly blocks that diabetes is a low-grade inflammatory disease. Only thosethe LPS induction of iNOS and COX-2 expression, which may drugs with slight or mild anti-inflammatory activities may beaccount for its anti-inflammatory mechanisms. able to prevent the development of diabetes.296 Xie and Du Volume 13 No. 4 April 2011
  9. 9. DIABETES, OBESITY AND METABOLISM review articleDiscussion and Perspectives chronic low-grade inflammation or preinflammatory state. Inflammatory cytokines, for example TNF-α, IL-1β, IL6,This review, firstly, indicates that most of TCM with hypo- NO, and so on, are released from macrophages and orglycaemic activities usually have separate anti-inflammatory other tissues during a state of inflammation (figure 2). Theseeffects, although their anti-inflammatory effects are weak factors can activate the IκB kinase (IKK)/JNK pathway,as compared with the classic anti-inflammatory drugs. In which results in the inhibition of insulin-receptor substrateaddition to routinely used hypoglycaemic Western/allopathic (IRS)/phosphatidylinositide 3-kinase (PI3K) pathway anddrugs, there are several Chinese hypoglycaemic herbs that brings about insulin resistance. The action of the IKK/JNKhave anti-inflammatory properties; this implies that we pathway also inhibits the production of pancreatic andneed to reunderstand the mechanism of action of these duodenal homeobox-1 (PDX-1)/MafA in pancreatic tissues andhypoglycaemic drugs, apart from the routine hypoglycaemic results in decreased insulin secretion. Therefore, inflammationmechanisms. In actuality, the aetiology of diabetes is still may promote the development of diabetes. Active componentsfar from fully proven. Indeed, diabetes is associated with a among traditional Chinese herbs with hypoglycaemic activities mainly comprise polysaccharides, terpenoids, flavonoids, and so on. Generally, these components have anti-inflammatory effects by their inhibition of TNF-α, IL-1β, IL-6, NO, and so on, release. The slight or moderate anti-inflammatory effects of TCM may be responsible for their hypoglycaemic mechanisms. This may contribute new evidences indicating that slight or moderate regulatory modulation by TCM on inflammation may be an effective tactic to prevent the development of diabetes. This review has provided different perspectives that reveal that diabetes may be an inflammatory disease and diverse TCM may share a common antidiabetic mechanism: anti- inflammatory action. Further research focusing on TCM in diabetes is required to validate these inflammation-regulating targets of TCM that may inhibit the development of diabetes. Acknowledgement This study was supported by the National Natural Science Foundation of China (81072680), Natural Science Foundation of Guangdong Province (2010), Tertiary College Science Foundation of Nanshan, Shenzhen (2008028) and the Science Seed Foundation (2008) of the Graduate School at Shenzhen, Tsinghua University, China. Conflict of Interest W. X. helped in data collection, analysis and paper writing. L. D. helped in design, data analysis and discussion. The authors have nothing to disclose. References 1. Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res Clin Pract 2003; 61S: S9–18. 2. Dorota Zozulinska, Bogna Wierusz-Wysocka. Type 2 diabetes mellitus as inflammatory disease. Diabetes Res Clin Pract 2006; 74S: S12–16. 3. Kato Y, Koide N, Komatsu T et al. Metformin attenuates production of nitric oxide in response to lipopolysaccharide by inhibiting MyD88- independent pathway. Horm Metab Res 2010; 42: 632–636. 4. Kawai T, Masaki T, Doi S et al. PPAR-gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-beta. LabFigure 2. Hypoglycaemic effects of traditional Chinese medicines (TCM) Invest 2009; 89: 47–58.mediated by mechanisms of anti-inflammatory action. ∗ Parts of the figure 5. Lamkanfi M, Mueller JL, Vitari AC et al. Glyburide inhibits the cryopy-were sourced from http://en.wikipedia.org/wiki. rin/Nalp3 inflammasome. J Cell Biol 2009; 187: 61–70.Volume 13 No. 4 April 2011 doi:10.1111/j.1463-1326.2010.01336.x 297
  10. 10. review article DIABETES, OBESITY AND METABOLISM 6. Yuan M, Konstantopoulos N, Lee J et al. Reversal of obesity- and diet- 26. Hartog A, Hougee S, Faber J et al. The multicomponent phytopharmaceu- induced insulin resistance with salicylates or targeted disruption of tical SKI306X inhibits in vitro cartilage degradation and the production of Ikkbeta. Science 2001; 293: 1673–1677. inflammatory mediators. Phytomedicine 2008; 15: 313–320. 7. Dandona P, Ghanim H, Bandyopadhyay A et al. Insulin suppresses 27. Yin J, Zhang H, Ye J. Traditional Chinese medicine in treatment of endotoxin induced oxidative, nitrosative and inflammatory stress in metabolic syndrome. Endocr Metab Immune Disord Drug Targets 2008; humans. Diabetes Care 2010; 33: 2416–2423. 8: 99–111. 8. Li WL, Zheng HC, Bukuru J, De Kimpe N. Natural medicines used in the 28. Ma SW, Benzie IF, Chu TT, Fok BS, Tomlinson B, Critchley LA. Effect of traditional Chinese medical system for therapy of diabetes mellitus. Panax ginseng supplementation on biomarkers of glucose tolerance, J Ethnopharmacol 2004; 92: 1–21. antioxidant status and oxidative stress in type 2 diabetic subjects: results of a placebo-controlled human intervention trial. Diabetes Obes Metab 9. Jia W, Gao WY, Tang LD. Antidiabetic herbal drugs officially approved in 2008; 10: 1125–1127. China. Phytother Res 2003; 17: 1127–1134. 29. Liu Z, Wang LJ, Li X et al. Hypoglycemic effects of malonyl-ginsenosides 10. Liu JP, Zhang M, Wang WY, Grimsgaard S. Chinese herbal medicines for extracted from roots of Panax ginseng on streptozotocin-induced diabetic type 2 diabetes mellitus. Cochrane Database Syst Rev 2004; 3: CD003642. mice. Phytother Res 2009; 23: 1426–1430. 11. Qi LW, Liu EH, Chu C et al. Anti-diabetic agents from natural products—an 30. Zhang Z, Li X, Lv W et al. Ginsenoside Re reduces insulin resistance update from 2004 to 2009. Curr Top Med Chem 2010; 10: 434–457. through inhibition of c-Jun NH2-terminal kinase and nuclear factor- 12. Wang E, Wylie-Rosett J. Review of selected Chinese herbal medicines in kappaB. Mol Endocrinol 2008; 22: 186–195. the treatment of type 2 diabetes. Diabetes Educ 2008; 34: 645–654. 31. Matsuda H, Samukawa K, Kubo M. Anti-inflammatory activity of ginseno- 13. Zhang JQ. Progress of diabetes research in traditional Chinese medicine side Ro. Planta Med 1990; 56: 19–23. in recent years. Zhong Xi Yi Jie He Xue Bao 2007; 5: 373–377. [Article in 32. Park S, Hong SM, Ahn IS, Kim YJ, Lee JB. Huang-Lian-Jie-Du-Tang supple- Chinese] mented with Schisandra chinensis Baill. And Polygonatum odoratum 14. Ren Y, Song CS, Liu XH, Shi Y, Gao JF, He XD. Experimental study on Druce improved glucose tolerance by potentiating insulinotropic actions compatible application of heat-clearing and detoxifying drugs with blood in islets in 90% pancreatectomized diabetic rats. Biosci Biotechnol circulation improving drugs. Zhongguo Zhong Yao Za Zhi 1994; 19: Biochem 2009; 73: 2384–2392. 626–628, 640. [Article in Chinese] 33. Zhang J, Shi LL, Zheng YN. Dibenzocyclooctadiene lignans from Fructus 15. Wang N, Zhang D, Mao X, Zou F, Jin H, Ouyang J. Astragalus polysaccha- Schisandrae Chinensis improve glucose uptake in vitro. Nat Prod Commun rides decreased the expression of PTP1B through relieving ER stress 2010; 5: 231–234. induced activation of ATF6 in a rat model of type 2 diabetes. Mol Cell 34. Guo LY, Hung TM, Bae KH et al. Anti-inflammatory effects of schisandrin Endocrinol 2009; 307: 89–98. isolated from the fruit of Schisandra chinensis Baill. Eur J Pharmacol 2008; 16. Zou F, Mao XQ, Wang N, Liu J, Ou-Yang JP. Astragalus polysaccharides 591: 293–299. alleviates glucose toxicity and restores glucose homeostasis in diabetic 35. Kako M, Miura T, Usami M, Kato A, Kadowaki S. Hypoglycemic effect of states via activation of AMPK. Acta Pharmacol Sin 2009; 30: 1607–1615. the rhizomes of ophiopogonis tuber in normal and diabetic mice. Biol 17. Liu M, Wu K, Mao X, Wu Y, Ouyang J. Astragalus polysaccharide improves Pharm Bull 1995; 18: 785–787. insulin sensitivity in KKAy mice: regulation of PKB/GLUT4 signaling in 36. Kou J, Sun Y, Lin Y et al. Anti-inflammatory activities of aqueous extract skeletal muscle. J Ethnopharmacol 2010; 127: 32–37. from Radix Ophiopogon japonicus and its two constituents. Biol Pharm 18. Li RJ, Qiu SD, Chen HX, Tian H, Wang HX. The immunotherapeutic effects Bull 2005; 28: 1234–1238. of Astragalus polysaccharide in type 1 diabetic mice. Biol Pharm Bull 37. Miura T, Ichiki H, Iwamoto N et al. Antidiabetic activity of the rhizoma of 2007; 30: 470–476. Anemarrhena asphodeloides and active components, mangiferin and its 19. Ryu M, Kim EH, Chun M et al. Astragali Radix elicits anti-inflammation glucoside. Biol Pharm Bull 2001; 24: 1009–1011. via activation of MKP-1, concomitant with attenuation of p38 and Erk. 38. Lu WQ, Qiu Y, Li TJ et al. Timosaponin B-II inhibits pro-inflammatory J Ethnopharmacol 2008; 115: 184–193. cytokine induction by lipopolysaccharide in BV2 cells. Arch Pharm Res 20. Zhang RX, Li MX, Jia ZP. Rehmannia glutinosa: review of botany, 2009; 32: 1301–1308. chemistry and pharmacology. J Ethnopharmacol 2008; 117: 199–214. 39. Hsu FL, Liu IM, Kuo DH, Chen WC, Su HC, Cheng JT. Antihyperglycemic 21. Huang WJ, Niu HS, Lin MH, Cheng JT, Hsu FL. Antihyperglycemic effect effect of puerarin in streptozotocin-induced diabetic rats. J Nat Prod of catalpol in streptozotocin-induced diabetic rats. J Nat Prod 2010; 73: 2003; 66: 788–792. 1170–1172. 40. Xiong FL, Sun XH, Gan L, Yang XL, Xu HB. Puerarin protects rat pancreatic 22. Waisundara VY, Huang M, Hsu A, Huang D, Tan BK. Characterization of islets from damage by hydrogen peroxide. Eur J Pharmacol 2006; 529: the anti-diabetic and antioxidant effects of Rehmannia glutinosa in 1–7. streptozotocin-induced diabetic Wistar rats. Am J Chin Med 2008; 36: 41. Yang X, Hu W, Zhang Q, Wang Y, Sun L. Puerarin inhibits C-reactive 1083–1104. protein expression via suppression of nuclear factor kappaB activation 23. Zhang R, Zhou J, Jia Z, Zhang Y, Gu G. Hypoglycemic effect of Rehman- in lipopolysaccharide-induced peripheral blood mononuclear cells of nia glutinosa oligosaccharide in hyperglycemic and alloxan-induced patients with stable angina pectoris. Basic Clin Pharmacol Toxicol 2010; diabetic rats and its mechanism. J Ethnopharmacol 2004; 90: 107: 637–642. 39–43. 42. Jing L, Cui G, Feng Q, Xiao Y. Evaluation of hypoglycemic activity of 24. Liu L, Tang L, Xu DS, Xia HL, Xie QM. Shengdi injection on rat model of the polysaccharides extracted from Lycium barbarum. Afr J Tradit lung inflammation induced by lipopolysaccharides. Zhongguo Zhong Yao Complement Altern Med 2009; 6: 579–584. Za Zhi 2007; 32: 526–528. [Article in Chinese] 43. MA LJ, Yang WB, Chen QL et al. The effect of Ly cium Barbarum 25. Hikino H, Yoshizawa M, Suzuki Y, Oshima Y, Konno C. Isolation and polysaccharide of function of endothelial cells and inflammatory reaction hypoglycemic activity of trichosans A, B, C, D, and E: glycans of in atherosclerosis. Liao NIng Zhong Yi Yao Zha Zhi 2005; 32: 1211–1213. Trichosanthes kirilowii roots. Planta Med 1989; 55: 349–350. [Article in Chinese]298 Xie and Du Volume 13 No. 4 April 2011
  11. 11. DIABETES, OBESITY AND METABOLISM review article 44. Li TH, Hou CC, Chang CL, Yang WC. Anti-hyperglycemic properties of crude 62. Chang YL, Chen CL, Kuo CL, Chen BC, You JS. Glycyrrhetinic acid inhibits extract and triterpenes from Poria cocos. Evid Based Complement Alternat ICAM-1 expression via blocking JNK and NF-kappaB pathways in TNF- Med 2011; 2011: pii: 128402. alpha-activated endothelial cells. Acta Pharmacol Sin 2010; 31: 546–553. 45. Sato M, Tai T, Nunoura Y, Yajima Y, Kawashima S, Tanaka K. Dehydro- 63. Kassaian N, Azadbakht L, Forghani B, Amini M. Effect of fenugreek seeds trametenolic acid induces preadipocyte differentiation and sensitizes on blood glucose and lipid profiles in type 2 diabetic patients. Int J Vitam animal models of noninsulin-dependent diabetes mellitus to insulin. Biol Nutr Res 2009; 79: 34–39. Pharm Bull 2002; 25: 81–86. 64. Uemura T, Hirai S, Mizoguchi N et al. Diosgenin present in fenugreek 46. Giner-Larza EM, Manez S, Giner-Pons RM, Carmen Recio M, Rı´os JL. On ´˜ improves glucose metabolism by promoting adipocyte differentiation the anti-inflammatory and anti-phospholipase A(2) activity of extracts and inhibiting inflammation in adipose tissues. Mol Nutr Food Res 2010; from lanostane-rich species. J Ethnopharmacol 2000; 73: 61–69. 54: 1596–1608. 47. Zhou J, Zhou S, Tang J et al. Protective effect of berberine on beta cells 65. Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, inva- in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic sion, and proliferation through the downregulation of Akt, I kappa B rats. Eur J Pharmacol 2009; 606: 262–268. kinase activation and NF-kappa B-regulated gene expression. Oncogene 2006; 25: 1463–1473. 48. Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism 66. Ooi CP, Yassin Z, Hamid TA. Momordica charantia for type 2 diabetes through induction of glycolysis. Am J Physiol Endocrinol Metab 2008; mellitus. Cochrane Database Syst Rev 2010; 2: CD007845. 294: E148–E156. 67. Miura T, Itoh C, Iwamoto N et al. Hypoglycemic activity of the fruit of the 49. Liu L, Yu YL, Yang JS et al. Berberine suppresses intestinal disaccharidases Momordica charantia in type 2 diabetic mice. J Nutr Sci Vitaminol (Tokyo) with beneficial metabolic effects in diabetic states, evidences from in 2001; 47: 340–344. vivo and in vitro study. Naunyn Schmiedebergs Arch Pharmacol 2010; 381: 371–381. 68. Klomann SD, Mueller AS, Pallauf J, Krawinkel MB. Antidiabetic effects of bitter gourd extracts in insulin-resistant db/db mice. Br J Nutr 2010; 9: 50. Remppis A, Bea F, Greten HJ et al. Rhizoma Coptidis inhibits LPS-induced 1–8. MCP-1/CCL2 production in murine macrophages via an AP-1 and NFkappaB-dependent pathway. Mediators Inflamm 2010; 2010: 194896. 69. Tan MJ, Ye JM, Turner N et al. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK 51. Hsu JH, Wu YC, Liu IM, Cheng JT. Dioscorea as the principal herb of Die- pathway. Chem Biol 2008; 15: 263–273. Huang-Wan, a widely used herbal mixture in China, for improvement of 70. Khanna P, Jain SC, Panagariya A, Dixit VP. Hypoglycemic activity of insulin resistance in fructose-rich chow-fed rats. J Ethnopharmacol 2007; polypeptide-p from a plant source. J Nat Prod 1981; 44: 648–655. 112: 577–584. 71. Kobori M, Nakayama H, Fukushima K et al. Bitter gourd suppresses 52. Kim MJ, Kim HN, Kang KS et al. Methanol extract of Dioscoreae Rhizoma lipopolysaccharide-induced inflammatory responses. J Agric Food Chem inhibits pro-inflammatory cytokines and mediators in the synoviocytes 2008; 56: 4004–4011. of rheumatoid arthritis. Int Immunopharmacol 2004; 4: 1489–1497. 72. Liu CT, Sheen LY, Lii CK. Does garlic have a role as an antidiabetic agent? 53. Lee SC, Tsai CC, Chen JC, Lin CC, Hu ML, Lu S. The evaluation of reno- and Mol Nutr Food Res 2007; 51: 1353–1364. hepatoprotective effects of huai-shan-yao (Rhizome Dioscoreae). Am J Chin Med 2002; 30: 609–616. 73. Liu CT, Hse H, Lii CK, Chen PS, Sheen LY. Effects of garlic oil and diallyl trisulfide on glycemic control in diabetic rats. Eur J Pharmacol 2005; 516: 54. Kato A, Miura T. Hypoglycemic activity of polygonati rhizoma in normal 165–173. and diabetic mice. Biol Pharm Bull 1993; 16: 1118–1120. 74. Hui C, Like W, Yan F, Tian X, Qiuyan W, Lifeng H. S-Allyl-L-cysteine 55. Kato A, Miura T, Yano H, Masuda K, Ishida H, Seino Y. Suppressive effects sulfoxide inhibits tumor necrosis factor-alpha induced monocyte adhesion of Polygonati rhizoma on hepatic glucose output, GLUT2 mRNA expression and intercellular cell adhesion molecule-1 expression in human umbilical and its protein content in rat liver. Endocr J 1994; 41: 139–144. vein endothelial cells. Anat Rec (Hoboken) 2010; 293: 421–430. 56. Peng C, Cao XY, Zeng Qing QH. Pharmacological study on the anti- 75. Ban JO, Oh JH, Kim TM et al. Anti-inflammatory and arthritic effects inflammatory effect of Polygonatum Polysaccharidi eye drops. Zhong of thiacremonone, a novel sulfur compound isolated from garlic via Yao Xin Yao Yu Lin Chuang Yao Li 1996; 7: 48–50. [Article in Chinese] inhibition of NF-kappaB. Arthritis Res Ther 2009; 11: R145. 57. Gong Z, Huang C, Sheng X et al. The role of tanshinone IIA in the ´ ´ 76. Trejo-Gonzalez A, Gabriel-Ortiz G, Puebla-Perez AM et al. A purified treatment of obesity through peroxisome proliferator-activated receptor extract from prickly pear cactus (Opuntia fuliginosa) controls experi- gamma antagonism. Endocrinology 2009; 150: 104–113. mentally induced diabetes in rats. J Ethnopharmacol 1996; 55: 27–33. 58. Zhang XP, Li ZJ, Liu DR. Progress in research into the mechanism of Radix 77. Park EH, Kahng JH, Lee SH, Shin KH. An anti-inflammatory principle from salviae miltiorrhizae in treatment of acute pancreatitis. Hepatobiliary cactus. Fitoterapia 2001; 72: 288–290. Pancreat Dis Int 2006; 5: 501–504. 78. Kim K, Kim H, Kwon J et al. Hypoglycemic and hypolipidemic effects of 59. Fan GW, Gao XM, Wang H et al. The anti-inflammatory activities of processed Aloe vera gel in a mouse model of non-insulin-dependent tanshinone IIA, an active component of TCM, are mediated by estrogen diabetes mellitus. Phytomedicine 2009; 16: 856–863. receptor activation and inhibition of iNOS. J Steroid Biochem Mol Biol 79. Rishi P, Rampuria A, Tewari R, Koul A. Phytomodulatory potentials of 2009; 113: 275–280. Aloe vera against Salmonella OmpR-mediated inflammation. Phytother 60. Ko BS, Jang JS, Hong SM et al. Changes in components, glycyrrhizin and Res 2008; 22: 1075–1082. glycyrrhetinic acid, in raw Glycyrrhiza uralensis Fisch, modify insulin 80. Akilen R, Tsiami A, Devendra D, Robinson N. Glycated haemoglobin sensitizing and insulinotropic actions. Biosci Biotechnol Biochem 2007; and blood pressure-lowering effect of cinnamon in multi-ethnic 71: 1452–1461. type 2 diabetic patients in the UK: a randomized, placebo-controlled, 61. Kuroda M, Mimaki Y, Sashida Y et al. Phenolics with PPAR-gamma ligand- double-blind clinical trial. Diabet Med 2010; 27: 1159–1167. doi: binding activity obtained from licorice (Glycyrrhiza uralensis roots) and 10.1111/j.1464-5491.2010.03079.x ameliorative effects of glycyrin on genetically diabetic KK-A(y) mice. 81. Ping H, Zhang G, Ren G. Antidiabetic effects of cinnamon oil in diabetic Bioorg Med Chem Lett 2003; 13: 4267–4272. KK-A(y) mice. Food Chem Toxicol 2010; 48: 2344–2349.Volume 13 No. 4 April 2011 doi:10.1111/j.1463-1326.2010.01336.x 299
  12. 12. review article DIABETES, OBESITY AND METABOLISM 82. Kwon KB, Kim EK, Jeong ES et al. Cortex cinnamomi extract prevents 101. Adisakwattana S, Moonsan P, Yibchok-Anun S. Insulin-releasing proper- streptozotocin- and cytokine-induced beta-cell damage by inhibiting ties of a series of cinnamic acid derivatives in vitro and in vivo. J Agric NF-kappaB. World J Gastroenterol 2006; 12: 4331–4337. Food Chem 2008; 56: 7838–7844. 83. Cao H, Graves DJ, Anderson RA. Cinnamon extract regulates glucose 102. Ma ZC, Hong Q, Wang YG et al. Ferulic acid attenuates adhesion molecule transporter and insulin-signaling gene expression in mouse adipocytes. expression in gamma-radiated human umbilical vascular endothelial Phytomedicine 2010; 17: 1027–1032. cells. Biol Pharm Bull 2010; 33: 752–758. 84. Tung YT, Chua MT, Wang SY, Chang ST. Anti-inflammation activities 103. Jung KJ, Go EK, Kim JY, Yu BP, Chung HY. Suppression of age-related renal of essential oil and its constituents from indigenous cinnamon changes in NF-kappaB and its target gene expression by dietary ferulate. (Cinnamomum osmophloeum) twigs. Bioresour Technol 2008; 99: J Nutr Biochem 2009; 20: 378–388. 3908–3913. 104. Lv L, Wu SY, Wang GF et al. Effect of astragaloside IV on hepatic glucose- 85. Kuroda M, Mimaki Y, Nishiyama T et al. Hypoglycemic effects of turmeric regulating enzymes in diabetic mice induced by a high-fat diet and (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice. Biol streptozotocin. Phytother Res 2010; 24: 219–224. Pharm Bull 2005; 28: 937–939. 105. Jiang B, Yang Y, Jin H et al. Astragaloside IV attenuates lipolysis and 86. Cheng TC, Lin CS, Hsu CC et al. Activation of muscarinic M-1 cholinocep- improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes. tors by curcumin to increase glucose uptake into skeletal muscle isolated Phytother Res 2008; 22: 1434–1439. from Wistar rats. Neurosci Lett 2009; 465: 238–241. 106. Zhang WJ, Hufnagl P, Binder BR, Wojta J. Antiinflammatory activity of 87. Funk JL, Frye JB, Oyarzo JN et al. Efficacy and mechanism of action of astragaloside IV is mediated by inhibition of NF-kappaB activation and turmeric supplements in the treatment of experimental arthritis. Arthritis adhesion molecule expression. Thromb Haemost 2003; 90: 904–914. Rheum 2006; 54: 3452–3464. 107. Kim T, Davis J, Zhang AJ, He X, Mathews ST. Curcumin activates AMPK and 88. Reay JL, Scholey AB, Milne A, Fenwick J, Kennedy DO. Panax ginseng has suppresses gluconeogenic gene expression in hepatoma cells. Biochem no effect on indices of glucose regulation following acute or chronic Biophys Res Commun 2009; 388: 377–382. ingestion in healthy volunteers. Br J Nutr 2009; 101: 1673–1678. 108. Kanitkar M, Gokhale K, Galande S, Bhonde RR. Novel role of curcumin in 89. Kim SK, Jung KH, Lee BC. Protective effect of tanshinone IIA on the early the prevention of cytokine-induced islet death in vitro and diabetogenesis stage of experimental diabetic nephropathy. Biol Pharm Bull 2009; 32: in vivo. Br J Pharmacol 2008; 155: 702–713. 220–224. 109. Nandal S, Dhir A, Kuhad A, Sharma S, Chopra K. Curcumin potentiates 90. Liu Y, Wang L, Li X, Lv C, Feng D, Luo Z. Tanshinone IIA improves impaired the anti-inflammatory activity of cyclooxygenase inhibitors in the cotton nerve functions in experimental diabetic rats. Biochem Biophys Res pellet granuloma pouch model. Methods Find Exp Clin Pharmacol 2009; Commun 2010; 399: 49–54. 31: 89–93. 91. Zhang Y, Wei L, Sun D et al. Tanshinone IIA pretreatment protects 110. Oh SW, Cha JY, Jung JE et al. Curcumin attenuates allergic airway myocardium against ischaemia/reperfusion injury through the phos- inflammation and hyper-responsiveness in mice through NF-kappaB phatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats. Dia- inhibition. J Ethnopharmacol 2010 [Epub ahead of print]. betes Obes Metab 2010; 12: 316–322. 111. Roghani M, Baluchnejadmojarad T. Hypoglycemic and hypolipidemic 92. Singh N, Gupta M. Regeneration of beta cells in islets of Langerhans of effect and antioxidant activity of chronic epigallocatechin-gallate in pancreas of alloxan diabetic rats by acetone extract of Momordica streptozotocin-diabetic rats. Pathophysiology 2010; 17: 55–59. charantia (Linn.) (bitter gourd) fruits. Indian J Exp Biol 2007; 45: 1055–1062. 112. Kim MK, Jung HS, Yoon CS et al. EGCG and quercetin protected INS-1 cells in oxidative stress via different mechanisms. Front Biosci (Elite Ed) 2010; 93. Harinantenaina L, Tanaka M, Takaoka S et al. Momordica charantia 2: 810–817. constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull (Tokyo) 2006; 54: 1017–1021. 113. Moon HS, Lee HG, Choi YJ, Kim TG, Cho CS. Proposed mechanisms of 94. Tanaka M, Misawa E, Ito Y et al. Identification of five phytosterols from (-)-epigallocatechin-3-gallate for anti-obesity. Chem Biol Interact 2007; Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull 2006; 29: 167: 85–98. 1418–1422. 114. Zheng Y, Toborek M, Hennig B. Epigallocatechin gallate-mediated protec- 95. Kobori M, Masumoto S, Akimoto Y, Takahashi Y. Dietary quercetin tion against tumor necrosis factor-α-induced monocyte chemoattractant alleviates diabetic symptoms and reduces streptozotocin-induced protein-1 expression is heme oxygenase-1 dependent. Metabolism 2010; disturbance of hepatic gene expression in mice. Mol Nutr Food Res 59: 1528–1535. 2009; 53: 859–868. 115. Bae HB, Li M, Kim JP et al. The effect of epigallocatechin gallate 96. Youl E, Bardy G, Magous R et al. Quercetin potentiates insulin secretion on lipopolysaccharide-induced acute lung injury in a murine model. and protects INS-1 pancreatic β-cells against oxidative damage via the Inflammation 2010; 33: 82–91. ERK1/2 pathway. Br J Pharmacol 2010; 161: 799–814. 116. Sharma S, Misra CS, Arumugam S et al. Antidiabetic activity of resvera- 97. Suchankova G, Nelson LE, Gerhart-Hines Z et al. Concurrent regulation of trol, a known SIRT1 activator in a genetic model for type-2 diabetes. AMP-activated protein kinase and SIRT1 in mammalian cells. Biochem Phytother Res 2011; 25: 67–73. Biophys Res Commun 2009; 378: 836–841. 117. Palsamy P, Subramanian S. Resveratrol, a natural phytoalexin, normalizes 98. Chirumbolo S. The role of quercetin, flavonols and flavones in modulating hyperglycemia in streptozotocin-nicotinamide induced experimental inflammatory cell function. Inflamm Allergy Drug Targets 2010; 9: diabetic rats. Biomed Pharmacother 2008; 62: 598–605. 263–285. 118. Palsamy P, Subramanian S. Ameliorative potential of resveratrol on 99. Tang D, Kang R, Xiao W et al. Quercetin prevents LPS-induced high- proinflammatory cytokines, hyperglycemia mediated oxidative stress, mobility group box 1 release and proinflammatory function. Am J Respir and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide- Cell Mol Biol 2009; 41: 651–660. induced diabetic rats. J Cell Physiol 2010; 224: 423–432.100. Ohnishi M, Matuo T, Tsuno T et al. Antioxidant activity and hypoglycemic 119. Wood LG, Wark PA, Garg ML. Antioxidant and anti-inflammatory effects effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice. of resveratrol in airway disease. Antioxid Redox Signal 2010; 13: Biofactors 2004; 21: 315–319. 1535–1548.300 Xie and Du Volume 13 No. 4 April 2011
  13. 13. DIABETES, OBESITY AND METABOLISM review article120. Kumar A, Sharma SS. NF-kappaB inhibitory action of resveratrol: a 131. Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN. Natural probable mechanism of neuroprotection in experimental diabetic and synthetic coumarin derivatives with anti-inflammatory/antioxidant neuropathy. Biochem Biophys Res Commun 2010; 394: 360–365. activities. Curr Pharm Des 2004; 10: 3813–3833.121. Chen WC, Hayakawa S, Yamamoto T, Huang LW, Liu IM, Cheng JT. The 132. Qian L, Xu Z, Zhang W, Wilson B, Hong JS, Flood PM. Sinomenine, a plasma glucose lowering action of tetrandrine in streptozotocin-induced natural dextrorotatory morphinan analog, is anti-inflammatory and diabetic rats. J Pharm Pharmacol 2004; 56: 643–648. neuroprotective through inhibition of microglial NADPH oxidase.122. Lieberman I, Lentz DP, Trucco GA, Seow WK, Thong YH. Prevention by J Neuroinflammation 2007; 4: 23. tetrandrine of spontaneous development of diabetes mellitus in BB rats. 133. Tang M, Guo Y, Zhou Y, Wu G. Effect of tripterysium glucosides on diabetic Diabetes 1992; 41: 616–619. cardiomyopathy in rats. Zhongguo Zhong Yao Za Zhi 2009; 34: 740–743.123. Wu SJ, Ng LT. Tetrandrine inhibits proinflammatory cytokines, iNOS and [Article in Chinese] COX-2 expression in human monocytic cells. Biol Pharm Bull 2007; 30: 134. Lu HM, Liang YZ, Yi LZ, Wu XJ. Anti-inflammatory effect of Houttuynia 59–62. cordata injection. J Ethnopharmacol 2006; 104: 245–249.124. Takii H, Kometani T, Nishimura T, Nakae T, Okada S, Fushiki T. Antidia- 135. Zheng P, Niu FL, Liu WZ, Shi Y, Lu LG. Anti-inflammatory mechanism of betic effect of glycyrrhizin in genetically diabetic KK-Ay mice. Biol Pharm oxymatrine in dextran sulfate sodium-induced colitis of rats. World Bull 2001; 24: 484–487. J Gastroenterol 2005; 11: 4912–4915.125. Yoshida T, Abe K, Ikeda T et al. Inhibitory effect of glycyrrhizin on 136. Liu L, Ning ZQ, Shan S et al. Phthalide lactones from Ligusticum lipopolysaccharide and d-galactosamine-induced mouse liver injury. Eur chuanxiong inhibit lipopolysaccharide-induced TNF-alpha production J Pharmacol 2007; 576: 136–142. and TNF-alpha-mediated NF-kappaB activation. Planta Med 2005; 71:126. Xue J, Ding W, Liu Y. Anti-diabetic effects of emodin involved in the 808–813. activation of PPARgamma on high-fat diet-fed and low dose of 137. Liao SL, Kao TK, Chen WY et al. Tetramethylpyrazine reduces ischemic streptozotocin-induced diabetic mice. Fitoterapia 2010; 81: 173–177. brain injury in rats. Neurosci Lett 2004; 372: 40–45.127. Feng Y, Huang SL, Dou W et al. Emodin, a natural product, selectively 138. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates glycemia and inflammatory parameters in obese young adults. Diabetes metabolic disorder in diet-induced obese mice. Br J Pharmacol 2010; Care 2008; 31: 289–294. 161: 113–126. 139. Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE128. Chen GL, Liu ZY, Wang J et al. Protective effect of emodin against and the TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 lipopolysaccharides-induced corneal injury in rats. Chin Med Sci J 2009; Diabetes) Study Team. The effects of salsalate on glycemic control in 24: 236–240. patients with type 2 diabetes: a randomized trial. Ann Intern Med 2010;129. Li HT, Wu XD, Davey AK, Wang J. Antihyperglycemic effects of baicalin on 152: 346–357. streptozotocin - nicotinamide induced diabetic rats. Phytother Res 2010 140. Lanas A, Tornero J, Zamorano JL. Assessment of gastrointestinal and [Epub ahead of print]. cardiovascular risk in patients with osteoarthritis who require NSAIDs:130. Liu LL, Gong LK, Wang H et al. Baicalin inhibits macrophage activation the LOGICA study. Ann Rheum Dis 2010; 69: 1453–1458. by lipopolysaccharide and protects micefrom endotoxin shock. Biochem 141. Bahar I, Rosenblat I, Erenberg M et al. Effect of dexamethasone eyedrops Pharmacol 2008; 75: 914–922. on blood glucose profile. Curr Eye Res 2007; 32: 739–742.Volume 13 No. 4 April 2011 doi:10.1111/j.1463-1326.2010.01336.x 301