Identification of potential immunomodulators from Pulsatilla decoction that act on therapeutic targets for ulcerative colitis based on pharmacological activity, absorbed ingredients, and in-silico molecular docking.

BACKGROUND: Pulsatilla decoction (Bai-Tou-Weng-Tang, BTWT) is a classic formula prescription of a traditional Chinese medicine that is used to treat ulcerative colitis (UC). However, its active components and underlying mechanism of action remain unclear. In the present study, we aimed to identify potential immunomodulators from BTWT that act at therapeutic targets for UC. METHODS: The protective effects of BTWT granules were examined in mice with colitis induced by dextran sulfate sodium. The absorbed components of BTWT were identified using LC-MS, and selected protein targets of these components in UC were investigated using molecular docking. RESULTS: Oral administration of BTWT granules significantly alleviated disease severity and colon shortening, and inhibited the inflammatory response in mice with chronic colitis. In these mice, 11 compounds from the BTWT granules were detected in the serum and/or colon. The molecular docking study demonstrated that compounds from Radix pulsatillae, such as anemoside A3, interacted with STAT3 and S1PR1; compounds from Rhizoma coptidis and/or Cortex phellodendri, such as palmatine, interacted with JAK3, PD-1, and PD-L1; and components of Cortex fraxini such as aesculin interacted with S1PR1, JAK3, STAT3 and PD-L1. Further in-vitro experiments showing that the compounds inhibited TNF-α and IL-6 production and STAT3 activation in RAW 264.7 cells suggested that these compounds have immunomodulatory activities. CONCLUSION: We revealed for the first time that 11 absorbed ingredients from BTWT were immunomodulators against therapeutic targets for UC. These findings suggest that the identified compounds are the active components of BTWT, and the identified protein targets underlie the mechanism of action of BTWT against UC.

Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota.

BACKGROUND: Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown. PURPOSE: To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action. METHODS: The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed. RESULTS: Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota. CONCLUSIONS: We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.

Anemoside B4 ameliorates experimental autoimmune encephalomyelitis in mice by modulating inflammatory responses and the gut microbiota.

BACKGROUND: Anemoside B4 (AB4) is a representative component of Pulsatilla decoction that is used in traditional Chinese medicine for treating inflammatory conditions. It is not known whether AB4 has beneficial effects on multiple sclerosis (MS). METHODS: In the present study, we examined the preventative and therapeutic effects of AB4, and the possible mechanism by which it protects female mice against experimental autoimmune encephalomyelitis (EAE). RESULTS: Preventative treatment with AB4 (given orally at 100 and 200 mg/kg for 18 days) reduced the clinical severity of EAE significantly (from 3.6 ± 1.3 to 1.8 ± 1.5 and 1.6 ± 0.6, respectively), and inhibited demyelination and inflammatory infiltration of the spinal cord. In the therapeutic protocol, oral administration of 200 mg/kg AB4 for 21 days after initiation of EAE significantly alleviated disease severity (from 2.6 ± 1.3 to 0.9 ± 0.6) and was as effective as the clinically used drug fingolimod (0.3 ± 0.6). Furthermore, both doses of AB4 significantly inhibited mRNA expression of TNF-α, IL-6, and IL-17, and STAT3 activation, in the spinal cord; and the ex vivo and iv vitro AB4 treatment markedly inhibited secretion of the three cytokines from lymphocytes of EAE mice upon in vitro restimulation. In addition, AB4 reversed the changes in the composition of the intestinal microbiome observed in EAE mice. CONCLUSION: We reveal for the first time that AB4 protects against EAE by modulating inflammatory responses and the gut microbiota, demonstrating that AB4 may have potential as a therapeutic agent for treating MS in humans.

The beneficial effects of Ganoderma lucidum on cardiovascular and metabolic disease risk.

CONTEXT: Various herbal medicines are thought to be useful in the management of cardiometabolic disease and its risk factors. Ganoderma lucidum (Curtis) P. Karst. (Ganodermataceae), also known as Lingzhi, has received considerable attention for various indications, including some related to the prevention and treatment of cardiovascular and metabolic disease by ameliorating major cardiovascular risk factors. OBJECTIVE: This review focuses on the major studies of the whole plant, plant extract, and specific active compounds isolated from G. lucidum in relation to the main risk factors for cardiometabolic disease. METHODS: References from major databases including PubMed, Web of Science, and Google Scholar were compiled. The search terms used were Ganoderma lucidum, Lingzhi, Reishi, cardiovascular, hypoglycaemic, diabetes, dyslipidaemia, antihypertensive, and anti-inflammatory. RESULTS: A number of in vitro studies and in vivo animal models have found that G. lucidum possesses antioxidative, antihypertensive, hypoglycaemic, lipid-lowering, and anti-inflammatory properties, but the health benefits in clinical trials are inconsistent. Among these potential health benefits, the most compelling evidence thus far is its hypoglycaemic effects in patients with type 2 diabetes or hyperglycaemia. CONCLUSIONS: The inconsistent evidence about the potential health benefits of G. lucidum is possibly because of the use of different Ganoderma formulations and different study populations. Further large controlled clinical studies are therefore needed to clarify the potential benefits of G. lucidum preparations standardised by known active components in the prevention and treatment of cardiometabolic disease.

Personalized medicine in lipid-modifying therapy.

The choice of lipid-modifying treatment is largely based on the absolute level of cardiovascular risk and baseline lipid profile. Statins are the first-line treatment for most patients requiring reduction of low-density-lipoprotein cholesterol (LDL-C) and ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors can be added to reach LDL-C targets. Statins have some adverse effects that are somewhat predictable based on phenotypic and genetic factors. Fibrates or omega-3 fatty acids can be added if triglyceride levels remain elevated. The RNA-targeted therapeutics in development offer the possibility of selective liver targeting for specific lipoproteins such as lipoprotein(a) and long-term reduction of LDL-C with infrequent administration of a small-interfering RNA may help to overcome the problem of adherence to therapy.

Impact of short-term bilberry supplementation on glycemic control, cardiovascular disease risk factors, and antioxidant status in Chinese patients with type 2 diabetes.

Bilberry (Vaccinium myrtillus L.) is one of the richest natural sources of anthocyanins which are powerful antioxidants and reported to have antiinflammatory, antidyslipidemic, antihypertensive, and hypoglycemic effects. The objective of this study was to assess the effect of bilberry supplementation on biomarkers of glycemic control, lipid profile, antioxidant, and inflammatory status in patients with type 2 diabetes in a randomized, double-blind, placebo-controlled cross-over study. Twenty patients were randomized to receive either bilberry supplementation (1.4 g/day of extract) daily for 4 weeks followed by 6 weeks of washout and then an additional 4 weeks of matching placebo or vice versa. Blood pressure, metabolic parameters, antioxidant status, and oxidative stress were measured before and after each period. Results showed no effect on body weight, blood pressure, or lipid profile. HbA1c was reduced by 0.31 ± 0.58% during bilberry supplementation, but this change was not significantly different from that with placebo. Antioxidant status, oxidative stress, and inflammatory status showed no significant differences across treatments. This short-term study of bilberry supplementation did not show significant effects on cardiovascular risk factors or antioxidant status, but the tendency for improved glycemic control may suggest a longer treatment period may be effective in diabetic patients.

Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk.

Metabolic syndrome is a cluster of interrelated conditions that is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Oxidative stress may impair normal physiological functions, leading to various illnesses. T2DM is considered to be associated with increased oxidative stress, inflammation, and dyslipidemia, which may play a significant role in the development of cardiovascular complications, cancer and vision loss through cataracts and retinopathy. While conventional therapies are a cornerstone for the management of the major risk factors of metabolic syndrome, increasing antioxidant defense by increasing intake of antioxidant-rich foods may improve long term prospects in CVD, obesity and T2DM. Bilberry (Vaccinium myrtillus L.) is one of the richest natural sources of anthocyanins which give berries their red/purple/blue coloration. Anthocyanins are powerful antioxidants and are reported to play an important role in the prevention of metabolic disease and CVD as well as cancer and other conditions. This review focuses on the potential effects of bilberry supplementation on metabolic and cardiovascular risk factors. Although there is evidence to support the use of bilberry supplementation as part of a healthy diet, the potential benefits from the use of bilberry supplementation in patients with T2DM or CVD needs to be clarified in large clinical trials.

Postprandial hyperlipidemia as a risk factor in patients with type 2 diabetes.

Introduction: Postprandial hyperlipidemia is a common feature of the atherogenic dyslipidemia in patients with type 2 diabetes. Quantification of this with oral fat tolerance tests is not used routinely in clinical practice and abnormal postprandial lipids are usually inferred from non-fasting plasma triglyceride levels. Identifying excessive postprandial hyperlipidemia may help to refine cardiovascular risk assessment but there are no treatments currently available which selectively target postprandial lipids and no large cardiovascular outcome trials using this as the entry criterion.Areas covered: In this review of relevant published material, we summarize the findings from the most important publications in this area.Expert opinion: Postprandial hyperlipidemia appears to contribute to the cardiovascular risk in patients with diabetes. Non-fasting triglyceride levels provide a surrogate marker of postprandial hyperlipidemia but more specific markers such as apoB48 levels may prove to be more reliable. Omega-3 fatty acids, fibrates and ezetimibe can reduce postprandial lipids but may not correct them completely. Several novel treatments have been developed to target hypertriglyceridemia and some of these may be particularly effective in improving postprandial levels. Further clinical trials are needed to establish the role of postprandial lipids in assessment of cardiovascular risk and to identify the most effective treatments.

A case of simvastatin-induced myopathy with SLCO1B1 genetic predisposition and co-ingestion of linagliptin and Stevia rebaudiana.

WHAT IS KNOWN AND OBJECTIVE: SLCO1B1 T521>C variant carriers are susceptible to simvastatin-induced myopathy. We report a patient who developed rhabdomyolysis possibly triggered by a drug-drug and/or herb-drug interaction. CASE DESCRIPTION: A 69-year-old man presented with myalgia and weakness progressing to severe rhabdomyolysis. He had been taking 40 mg simvastatin daily for 10 years and recently consumed supplements, including Stevia rebaudiana and linagliptin. Genotyping revealed he carried one copy of SLCO1B1 T521>C and two copies of ABCG2 C421>A. WHAT IS NEW AND CONCLUSION: Despite apparent long-term safe administration, co-ingestion of simvastatin and other CYP3A4 inhibitors may result in severe myopathy in those at increased genetic risk.

The adjuvant value of Herba Cistanches when used in combination with statin in murine models.

Statins are well known to have muscle toxicity problem. Herba Cistanches (HC) is a Chinese herb traditionally used for pain in the loins and knees. Our previous in vitro study suggested that it could protect against statin-induced muscle toxicity. However, its in vivo protective effect has never been investigated. The objective of this study was to determine if the aqueous extract of HC (HCE) could prevent simvastatin-induced muscle toxicity in rats, and whether HCE could also exert beneficial effects on reducing high-fat diet-induced hypercholesterolemia and elevated liver cholesterol, thereby reducing the dose of simvastatin when used in combined therapy. From our results, HCE significantly restored simvastatin-induced reduction in muscle weights and reduced elevated plasma creatine kinase in rats. HCE also improved simvastatin-induced reduction in muscle glutathione levels, muscle mitochondrial membrane potential, and reduced simvastatin-induced muscle inflammation. Furthermore, HCE could exert reduction on liver weight, total liver lipid levels and plasma lipid levels in high-fat-fed mice. In conclusion, our study provided in vivo evidence that HCE has potential protective effect on simvastatin-induced toxicity in muscles, and also beneficial effects on diet-induced non-alcoholic fatty liver and hyperlipidemia when being used alone or in combination with simvastatin at a reduced dose.

The protective effect of Herba Cistanches on statin-induced myotoxicity in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Cistanches (HC, Cistanche deserticola or Cistanche tubulosa) is a Chinese herb traditionally used for muscle problems. Previous studies demonstrated that HC extract could reduce muscle damage and improve ATP storage in post-exercised rats. However, its effect on statin-induced muscle toxicity has never been investigated. AIM: The objective of this study was to determine if the aqueous extract of HC (HCE) could prevent simvastatin-induced toxicity in L6 rat skeletal muscle cells; and whether verbascoside is the major bioactive constituent which contributes to the effects. MATERIALS AND METHODS: MTT was performed to determine the effects of HCE (0-2000µg/ml) or verbascoside (0-160µM) on simvastatin (10µM)-treated L6 cells. Annexin V-FITC/PI apoptosis assay and Caspase 3 assay were performed to determine the protective role of HCE on simvastatin-induced cell death, and to evaluate if HCE exerted its protective effect through the caspase pathway. ATP production was measured to investigate if HCE could prevent simvastatin-induced reduction in ATP production in vitro. RESULTS: Simvastatin significantly increased apoptotic cell death in L6 cells. HCE significantly exerted a dose-dependent reduction on simvastatin-induced apoptotic cells, possibly via caspase-3 pathway. Simvastatin reduced the ATP production in L6 cells, which was dose-dependently prevented by HCE. There was only a trend but not significant effect (except at high dose) of verbascoside on the protection of simvastatin-induced muscle toxicity. CONCLUSIONS: In conclusion, we demonstrated for the first time that HCE could exert dose-dependent protective effect on simvastatin-induced toxicity in vitro, which was unlikely due to the presence of verbascoside. Our study suggested the potential use of HC under the situation of simvastatin-induced muscle toxicity.

Evaluation of a crataegus-based multiherb formula for dyslipidemia: a randomized, double-blind, placebo-controlled clinical trial.

Background. We for the first time examined the effects of a multiherb formula containing Crataegus pinnatifida (1 g daily), Alisma orientalis, Stigma maydis, Ganoderma lucidum, Polygonum multiflorum, and Morus alba on plasma lipid and glucose levels in Chinese patients with dyslipidemia. Methods. In this randomized, double-blind, placebo-controlled study, 42 patients were randomized at a ratio of 1 : 1 to receive the herbal formula or placebo for 12 weeks and 40 patients completed the study. Lipid profiles, glucose, glycated haemoglobin (HbA1c), and laboratory safety parameters were performed before and after treatment. Results. The difference in the changes in low-density lipoprotein cholesterol (LDL-C) levels between placebo and active treatment (-9%) was significantly (P < 0.05) better with active treatment. HbA1c levels significantly decreased by -3.9% in the active treatment group, but the change was not significantly different from that with placebo (-1.1%) (P = 0.098). There were no apparent adverse effects or changes in laboratory safety parameters with either treatment. Conclusions. The multiherb formula had mild beneficial effects on plasma LDL-C after 12-weeks treatment in subjects with dyslipidemia without any noticeable adverse effects.

Bench to bed evidences for pharmacokinetic and pharmacodynamic interactions involving oseltamivir and chinese medicine.

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although C max, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P < 0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P < 0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe.

Whole soy, but not purified daidzein, had a favorable effect on improvement of cardiovascular risks: a 6-month randomized, double-blind, and placebo-controlled trial in equol-producing postmenopausal women.

SCOPE: Equol is produced by the intestinal bacteria from isoflavone daidzein. Studies have reported the health benefits of soy can only present or more pronounced in equol producers. This 6-month randomized controlled trial examined the effect of whole soy (soy flour) and purified daidzein on cardiovascular biomarkers and carotid intima-media thickness (CIMT) in prehypertensive postmenopausal women who were equol producers. METHODS AND RESULTS: Two hundred seventy eligible women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting venous samples were obtained at baseline and end of trial for testing glucose, lipids, high sensitivity C-reactive protein (hs-CRP), and free fatty acid. Changes in common CIMT were also assessed. Serum LDL-C decreased by 7.95% (95% CI: -15.09∼-0.81%) and 6.32% (95% CI: -13.45∼0.08%), and serum hs-CRP decreased by 0.164 (95% CI: -0.309∼-0.019) and 0.054 (95% CI: -0.199∼0.012) in the whole soy group compared with daidzein and milk placebo groups, respectively. No significant change in CIMT was found. CONCLUSION: Whole soy, but not purified daidzein, had a beneficial effect on reduction of LDL-C and hs-CRP among prehypertensive equol-producing postmenopausal women.

Evaluation of the pharmacokinetics and drug interactions of the two recently developed statins, rosuvastatin and pitavastatin.

INTRODUCTION: Statins are the cornerstone of lipid-lowering therapy to reduce the risk of coronary heart disease. Rosuvastatin and pitavastatin are the two recently developed statins with less potential for drug interaction resulting in improved safety profiles. AREAS COVERED: This review summarizes the pharmacokinetics and drug interactions of rosuvastatin and pitavastatin. The materials reviewed were identified by searching PubMed for publications using 'rosuvastatin', 'pitavastatin', 'statins', 'pharmacokinetics' and 'drug interaction' as the search terms. EXPERT OPINION: Rosuvastatin and pitavastatin have favorable pharmacokinetic and safety profiles as their disposition does not depend on or is only marginally influenced by cytochrome P450 (CYP) enzymes, thus potentially reducing the risk of drug-drug interactions of these two statins with other drugs known to inhibit CYP enzymes. However, drug transporters play a significant role in the disposition of rosuvastatin and pitavastatin and drug interactions may occur through these. Genetic polymorphisms in drug transporters may also affect the pharmacokinetics, drug interactions and/or the lipid-lowering effect of these statins to a different extent.

Effects of grapefruit juice and SLCO1B1 388A>G polymorphism on the pharmacokinetics of pitavastatin.

Pitavastatin undergoes little hepatic metabolism but it is a substrate for uptake and efflux transporters, particularly OATP1B1 (gene SLCO1B1). A previous study in 8 Japanese healthy subjects showed that co-administration with grapefruit juice (GFJ) resulted in a small increase in systemic exposure to pitavastatin. We examined whether common polymorphisms in SLCO1B1 might influence the pharmacokinetics of pitavastatin or the interaction with GFJ. Twelve Chinese healthy male volunteers took pitavastatin 2 mg orally with water or with GFJ on separate occasions and plasma concentrations of pitavastatin acid and lactone were measured over 48 h. GFJ increased the mean area under the plasma concentration-time curve (AUC0-48 h) for both pitavastatin acid and lactone by 14% (p<0.05). Subjects with SLCO1B1 *1b/*1b haplotype (388GG-521TT) had 47% and 44% higher systemic exposure for pitavastatin acid and lactone than the SLCO1B1 *1a carriers (388AA/AG-521TT, p<0.05 and p=0.005, respectively). The SLCO1B1 388A>G polymorphism, which increases transporter activity for some statins, was associated with higher plasma levels of pitavastatin acid and lactone in subjects with the homozygous variant indicating decreased hepatic uptake. Co-administration of pitavastatin with GFJ resulted in a small but significant increase in plasma levels in healthy Chinese subjects.

Theranostics meets traditional Chinese medicine: rational prediction of drug-herb interactions.

Herbal medicines including traditional Chinese medicine are becoming increasingly more popular worldwide. However, there is considerable potential for interaction between herbal components and drugs, as all herbal medicines contain a combination of potentially biologically active compounds possessing various inherent pharmacological activities, and the components of herbal products consumed are eliminated from the body by the same mechanisms that remove drugs. Indeed, many so-called conventional drugs are derived from plant sources. This article provides an update on the mechanisms and evidence of drug-herb interactions (DHIs) and genetic influences on DHIs. The rational prediction of clinically important DHIs is also discussed. Individualized and targeted drug therapy could be achieved by identifying the population most likely to be helped or harmed by drug-herb coadministration.

Study of the effects of total flavonoids of Astragalus on atherosclerosis formation and potential mechanisms.

Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.

Hyperglycaemia and vitamin D: a systematic overview.

Vitamin D plays a role in a range of functions that may impact on glycaemic control. In this study we systematically report on clinical studies evaluating the impact of vitamin D on aspects of hyperglycaemia in non-pregnant adults. A total of 1,294 articles, of which 417 were reviews, were identified. No well-designed randomised, controlled trials were identified that specifically investigated the effects of vitamin D supplementation on glucose and insulin concentrations. The majority of the studies that are available were poorly designed, having limited numbers, short study duration, or were conducted in volunteers with normal baseline, as measured by 25-hydroxyvitamin D (25(OH)D), concentrations or used inadequate doses of the supplements to normalise vitamin D concentrations, or used inappropriate analyses. Most studies did not observe improvements in glycaemia, with few exceptions. The results were more equivocal for aspects of insulin resistance. Most found no benefit on measures of insulin resistance, although some did. However, more studies described improved insulin release, although data from the studies to date are really inadequate to provide any reliable conclusions. Well-conducted randomised, controlled trials with adequate vitamin D doses are required to effectively assess whether this vitamin can reduce the incidence of diabetes.

Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial.

Previous studies have suggested that Lingzhi (Ganoderma lucidum) has antioxidant effects and possibly beneficial effects on blood pressure, plasma lipids and glucose, but these have not been confirmed in subjects with mild hypertension or hyperlipidaemia. The objective of the present study was to assess the cardiovascular, metabolic, antioxidant and immunomodulatory responses to therapy with Lingzhi in patients with borderline elevations of blood pressure and/or cholesterol in a controlled cross-over trial. A total of twenty-six patients received 1·44 g Lingzhi daily or matching placebo for 12 weeks in a randomised, double-blind, cross-over study with placebo-controlled run-in and cross-over periods. Body weight, blood pressure, metabolic parameters, urine catecholamines and cortisol, antioxidant status and lymphocyte subsets were measured after each period. Lingzhi was well tolerated and data from twenty-three evaluable subjects showed no changes in BMI or blood pressure when treated with Lingzhi or placebo. Plasma insulin and homeostasis model assessment-insulin resistance were lower after treatment with Lingzhi than after placebo. TAG decreased and HDL-cholesterol increased with Lingzhi but not with placebo in the first treatment period, but significant carry-over effects prevented complete analysis of these parameters. Urine catecholamines and cortisol, plasma antioxidant status and blood lymphocyte subsets showed no significant differences across treatments. Results indicate that Lingzhi might have mild antidiabetic effects and potentially improve the dyslipidaemia of diabetes, as shown previously in some animal studies. Further studies are desirable in patients with hyperglycaemia.