The dual actions of Sanmiao wan as a hypouricemic agent: Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice

Ethnopharmacological relevance

Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine.

Aim of the study

The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice.

Materials and methods

SMW at 489, 978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5 mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.

Results

SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice.

Conclusion

These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemic mice.     

Anti-hyperuricemic and nephroprotective effects of Modified Simiao Decoction in hyperuricemic mice

Ethnopharmacological relevance

Modified Simiao Decoction (MSD), based on clinical experience, has been used for decades and famous for its efficiency in treating hyperuricemic and gouty diseases.

Aim of the study

To investigate the effects of MSD on anti-hyperuricemic and nephroprotective effects are involved in potassium oxonate-induced hyperuricemic mice.

Materials and methods

The effects of MSD were investigated in hyperuricemic mice induced by potassium oxonate. MSD were fed to hyperuricemic mice daily at a dose of 0.45, 0.90, 1.80 g/kg for 10 days, and allopurinol (5 mg/kg) was given as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were determined by colorimetric method. Its nephroprotective effects were evaluated by determining a panel of oxidative stress markers after the intervention in hyperuricemic mice. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the kidney were analyzed by Western blotting.

Results

MSD could inhibit XOD activities in serum and liver, decrease levels of serum uric acid, serum creatinine and BUN, and increased levels of urine uric acid, urine creatinine, FEUA dose-dependently through down-regulation of URAT1 and up-regulation of OAT1 protein expressions in the renal tissue of hyperuricemic mice. It also effectively reversed oxonate-induced alterations on renal MDA levels and SOD activities in this model.

Conclusion

MSD processes uricosuric and nephroprotective actions by regulating renal urate transporters and enhancing antioxidant enzymes activities to improve renal dysfunction in hyperuricemic mice.     

Anti-urolithiatic effects of Punica granatum in male rats

Ethnopharmacological relevance

The traditional use of Punica granatum has been reported to regulate urine discharge and controls the burning sensation of urine.

Materials and methods

Animals model of calcium oxalate urolithiasis was developed in male rats by adding ethylene glycol 0.75% in drinking water. The Punica granatum chloroform extract (PGCE) and Punica grantum methanol extract (PGME) orally at 100, 200 and 400 mg/kg, respectively, were administered along with ethylene glycol for 28 days. On 28 day, 24 h urine was collected from individual rats and used for estimation of urine calcium, phosphate and oxalate. The serum creatinine, urea and uric acid levels were estimated in each animal. The kidney homogenate was used for the estimation of renal oxalate contents. The paraffin kidney sections were prepared to observe the CaOx deposits.

Results

The ethylene glycol control (Gr.-II) had significant (P < 0.001 vs. normal) increase in levels of urine oxalate, calcium and phosphate, serum creatinine, urea and uric acid and renal tissues oxalates, as compared to normal (Gr.-I). The paraffin kidney sections show significant histopathological changes. The treatment of PGCE and PGME at 100, 200 and 400 mg/kg doses, significantly (P < 0.001 vs. control) decreased the urine oxalate, calcium and phosphate, renal tissue oxalates and serum creatinine, urea and uric acid, in EG induced urolithiasis after 28 days.

Conclusions

The PGCE and PGME at the doses of 400 mg/kg, found to be more effective in decreasing the urolithiasis and regeneration of renal tissues in male rats.     

Inhibitory effect of Coptis chinensis on inflammation in LPS-induced endotoxemia

Ethnopharmacological relevance

Rhizoma coptidis (RC) has been used as a remedy for inflammation-related diseases in traditional medicine. Although it is known to have anti-inflammatory activities, its mechanism of action on lipopolysaccharide (LPS)-induced inflammation has not yet been identified in detail.

Aim of the study

This study was designed to assess the beneficial effects of pretreatment with RC in ameliorating LPS-induced liver inflammation.

Materials and methods

Mice were orally administered RC (500, 1000 mg/kg) for three days in a row. 1 h after the last RC administration, the mice were intraperitoneally injected with LPS (35 mg/kg). After treatment, histological alterations and inflammatory factor levels in the liver and proinflammatory cytokines in the serum associated with inflammation were examined.

Results

We found that pretreatment with RC (500 and 1000 mg/kg) exerted a significant protective effect by attenuating liver histopathological changes in endotoxemic mice. The results also demonstrated that RC suppressed secretion of LPS-stimulated pro-inflammatory cytokines, such as interleukin-6 (IL-6). Furthermore, RC inhibited LPS-mediated nuclear factor (NF)-κB activation via the prevention of IκB-α phosphorylation, as well as the phosphorylation of ERK1/2, JNK, and p38 MAPKs. These results were associated with decreases in the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (I-NOS).

Conclusions

The results presented here clearly demonstrate that RC could significantly protect mice against LPS-induced acute liver injury.     

Anti-fatigue effects of proteins isolated from Panax quinquefolium

Ethnopharmacological relevance

American ginseng (Panax quinquefolium) is an obligate shade perennial plant that belongs to Araliaceae ginseng species, and is native to eastern USA and Canada. Ginseng proteins are reported to have several pharmaceutical properties. However, such properties of American ginseng proteins (AGP) have seldom been reported. Also, anti-fatigue properties of AGP have not been studied. Therefore, we examined the anti-fatigue effects of AGP in mice.

Materials and methods

The molecular weight and protein contents of AGP were determined by SDS-PAGE, while the amino acid composition was analyzed by HPLC. The mice were divided into four groups. The control group was administered distilled water by gavage every day for 28 days. The other groups, designated as AGP treatment groups, were administered 125, 250 and 500 mg/kg of body weight, respectively of AGP by gavage every day for 28 days. Anti-fatigue activity was estimated using forced swimming test, and biochemical indices were determined using available kits.

Results

The subunit molecular weight of AGP ranged from 8–66 kD and the protein content measured by Bradford assay was 1.86 mg/mL. The forced swimming time of low, intermediate and high groups were found to be longer as compared to the control group. AGP significantly decreased blood lactate (BLA) and serum urea nitrogen (SUN) levels, and increased hepatic glycogen (GLU) level. Additionally, AGP lowered malondialdehyde (MDA) content and increased the levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD).

Conclusion

AGP shows anti-fatigue activity in mice, as measured by the physiological indices for fatigue.     

Antinociceptive activity of Rhoifoline A from the ethanol extract of Zanthoxylum nitidum in mice

Aim of the study

Antinociceptive activity of Rhoifoline A (RA), a benzophenanthridine alkaloid obtained from the ethanol extract of Zanthoxylum nitidum, was evaluated in mice using chemical and thermal models of nociception.

Materials and methods

RA was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception.

Results

RA administered intraperitoneally at doses of 10, 20, 40 and 80 mg/kg exhibited significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin, and on thermal nociception in the tail-flick test and the hot plate test. RA neither significantly impaired motor coordination in the rotarod test nor did spontaneous locomotion in the open-field test. RA did not enhance the pentobarbital sodium induced sleep time. These results indicated that the observed antinociceptive activity of RA was unrelated to sedation or motor abnormality. Core body temperature measurement showed that RA did not affect temperature during a 2-hour period. Furthermore, RA-induced antinociception in the hot plate test was insensitive to naloxone or glibenclamide but significantly antagonized by L-NAME, methylene blue and nimodipine.

Conclusions

Therefore, it is reasonable that the analgesic mechanism of RA possibly involved the NO-cGMP signaling pathway and L-type Ca²⁺ channels.     

Hepatoprotective and antioxidant effects of Myelophil on restraint stress-induced liver injury in BALB/c mice

Ethnopharmacologic relevance

Myelophil, an ethanol extract of Astragali Radix and Salviae Radix, has been used for patients with chronic fatigue-associated disorders in traditional Oriental clinics.

Aim of the study

This study aimed to evaluate the pharmacologic effects of Myelophil using a restraint stress-induced liver injury model and to explore the mechanisms underlying these effects.

Materials and methods

Distilled water or Myelophil (50 mg/kg, 100 mg/kg, or 200 mg/kg) was orally administered to 6-week-old BALB/c male mice once daily for 5 day. The mice were subjected to restraint stress for 6 h, and serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively), total reactive oxygen species, and total antioxidant capacity were determined. Hepatic tissue levels of lipid peroxidation, antioxidant activity (as represented by superoxide dismutase, catalase, and glutathione reductase activity), and interleukin-1 were also measured.

Results

Restraint stress induced severe oxidative stress and hepatic injury, as evidenced by marked elevation of serum ALT and AST levels, increased levels of reactive oxygen species and lipid peroxidation activity, and depletion of antioxidant enzyme activities. Myelophil pretreatment significantly attenuated not only the elevation of serum ALT and AST but also the increase in reactive oxygen species and lipid peroxidation. It also restored a significant fraction of the catalase, glutathione reductase, and peroxidase activity in liver tissues. Myelophil pretreatment also partially normalized the levels of interleukin-1β gene and protein expression.

Conclusions

These results suggest that Myelophil has potent protective effects against restraint stress-induced liver injury via antioxidant activities, and have relevance to the clinical applications of Myelophil in field of traditional herbal medicine.     

Antinociceptive activity of aqueous extract and isolated compounds of Lithrea molleoides

Ethnopharmacological relevance

Lithrea molleoides (Vell.) Engl. (Anacardiaceae) is a medicinal plant commonly used in traditional medicine in South America.

Aim of the study

In the present study, the in vivo antinociceptive effect of L. molleoides' aqueous extract and its isolated compounds has been investigated.

Materials and Methods

Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed.

Results

The extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) and formalin (ED50: 7.7 mg/kg, i.p.) administered intraperitoneally and also orally. Yohimbine diminished the activity of the extract in the acetic acid test meanwhile haloperidol enhanced its effect. Two majority compounds, shikimic and vanillic acid were active in chemical nociceptive models used in this work, producing the highest inhibition of the writhing response at a dose of 30 mg/kg i.p. (55.4% and 57.1%, respectively) meanwhile at 100 mg/kg p.o. produced a slight response (23.3% and 23.9%, respectively).

Conclusions

These results suggest that L. molleoides' aqueous extract produced antinociception possibly related to the presence of shikimic and vanillic acid. The adrenergic and dopaminergic systems seem to be involved in the mechanism of antinociception of the extract.     

Mechanism of protective effects of Danshen against iron overload-induced injury in mice

Ethnopharmacological relevance

Danshen (Salvia miltiorrhiza) has been widely prescribed in traditional folk medicine for treatment of hepatic and cardiovascular diseases in China and other Asian countries for several hundred years.

Materials and methods

Sixty male mice were randomly divided into five groups: control, iron overload, low-dose Danshen (L-Danshen, 3 g/kg/day), high-dose Danshen (H-Danshen, 6 g/kg/day) and deferoxamine (DFO) groups (n=12 per group). Iron dextran was injected intraperitoneally (i.p.) at 50 mg/kg body weight/day to establish the iron overload model. While control mice received saline, mice of the treated groups simultaneously received (i.p.) injections of L-Danshen, H-Danshen or DFO daily for 2 weeks. At the end of the experiment, changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), glutathione peroxidase (GSH-Px), superoxide desmutase (SOD) and malondialdehyde (MDA) were measured, and histological changes were observed by Prussian blue or hematoxylin and eosin staining of the liver. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling.

Results

Treatment of iron overloaded mice with either low or high doses of Danshen not only significantly attenuated the hepatic dysfunction (ALT/AST levels), decreased the content of MDA and increased the activities of GSH-Px and SOD, it also suppressed apoptosis in hepatocytes. Histopathological examination showed that treatment with Danshen reduced iron deposition and ameliorated pathological changes in the liver of iron overloaded mice.

Conclusions

Danshen demonstrated significant protective effects in the liver of iron overloaded mice, which were at least partly due to the decrease of iron deposition and inhibition of lipid peroxidation and hepatocyte apoptosis.     

Effect of Qilongtoutong granule on calcitonin gene-related peptide,beta-endorphin,serotonin, dopamine,and noradrenalin in migraine model rats and mice

Objective

To study the effect of Qilongtoutong granule (QLTT) on plasma calcitonin gene-related peptide (CGRP), beta-endorphin (β-EP), 5-HT, dopamine (DA), noradrenalin (NE), and blood viscosity in migraine model rats and mice.

Methods

Both the acute blood stasis model group and nitroglycerin-induced migraine model group included 60 Sprague-Dawley rats. The reserpine-reduced model group had 60 Kunming mice. Rats from each test were grouped into normal control group, model group, Zhengtian pill (ZTP) group, and high, moderate, or low-dose QLTT groups. In the acute blood stasis model test, after gavage for 7 days, rats were given 0.8 mL/kg adrenaline hydrochloride subcutaneously twice, and kept in ice water for 5 min. After fasting for 12 h, rats were anesthetized and blood samples were collected for detection of blood viscosity. In the nitroglycerin-induced migraine group, after gavage for 7 days, rats were intraperitoneally injected nitroglycerin (10 mg/kg), and 4 h later, blood samples were collected from postcava for measuring the plasma CGRP and β-EP levels. In the reserpine-reduced model test, except the normal control group, mice were administered reserpine (0.25 mg/kg, i.h.) for 9 days. Mice received intragastric administration from the third day to the ninth day. One hour after the last gavage, blood and brain tissue samples were obtained. Then, blood clotting time and the contents of neurotransmitters were determined.

Results

QLTT- (3.6, 1.8, and 0.9 g/kg) and ZTP-treated rats had lower blood viscosity than that in model rats under different shear rates (P< 0.01). QLTT- (3.6, 1.8 g/kg) and ZTP-treated rats had significantly lower plasma CGRP levels and higher plasma β-EP levels than those in model rats (P< 0.01). QLTT treatment at dose of 0.9 g/kg had lower plasma CGRP levels as well (P<0.05). QLTT- (5.2, 2.6 g/kg) and ZTP-treated mice had longer blood clotting time than that in model mice (P<0.01). QLTT- (2.6 g/kg) and ZTP-treated mice had higher plasma serotonin (5-HT) levels than those in model mice (P<0.05).

Conclusion

QLTT-treated animals had lower plasma CGRP level, higher plasma β-EP, 5-HT, higher brain tissue 5-HT, NE, DA levels, and lower blood viscosity than those in the migraine model animals.     

Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal (HPA) axis in a chronic cold-stress mouse model

Ethnopharmacological relevance

Myelophil is composed of Astragali Radix and Salviae Miltiorrhizae Radix, according to the long traditional pharmacological practices, and it has been used for patients with chronic fatigue-associated symptoms including concentration problem or memory loss.

Aim of the study

This study aimed to evaluate the clinical relevance of Myelophil on brain oxidative damage using a chronic cold stress mice model.

Material and methods

Balb/c mice were subjected to cold stress (4 °C for 4 h) six times per week for 2 weeks with or without oral administration of Myelophil (50, 100, or 200 mg/kg), or ascorbic acid (50 mg/kg).

Results

Chronic cold stress induced histopathological hippocampal apoptosis with drastically increased serum levels of total reactive oxygen species and nitric oxide, as well as brain lipid peroxidation levels, protein carbonyl, and caspase-3/7 activity. These alterations were significantly ameliorated by Myelophil treatment. Myelophil administration significantly recovered the depleted glutathione and its enzymes, superoxide dismutase activity, and catalase protein and gene expression levels. Serum levels of corticosterone, dopamine, and adrenaline were notably altered by chronic cold stress but were significantly ameliorated by Myelophil treatment. Myelophil also normalized alterations in tumor necrosis factor-α, interleukin (IL)-1β, and IL-10 gene expression and protein levels. Chronic cold stress up-regulated gene expression levels of phenylethanolamine N-methyltransferase and monoamine oxidase-B, and glucocorticoid receptors in the hypothalamus and hippocampus, respectively, whereas Myelophil treatment completely normalized these levels.

Conclusions

These results suggest that Myelophil has potent pharmaceutical effects against chronic cold-stress-induced brain damage by relieving oxidative stress and inflammation and regulating stress hormones in mice.     

Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo

Ethnopharmacological relevance

The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE).

Aim of the study

To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo.

Materials and methods

Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice.

Results

AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC₅₀ of 0.41 μg/ml, and 100 mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice.

Conclusions

Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications.     

Anti-atherosclerosis and hyperlipidemia effects of herbal mixture, Artemisia iwayomogi Kitamura and Curcuma longa Linne,in apolipoprotein E-deficient mice

Ethnopharmacolgical relevance

Artemisiaiwayomogi Kitamura and Curcuma longa Linne. (ACE) has been popularly used to treat atherosclerosis as well as hyperlipidemia in the Asian countries.

Objective

Antiatherosclerotic and anti-hyperlipidemic effects of ACE were evaluated at protein and gene expression level by using apoE^−/− mice.

Method

Apoprotein E deficient (apoE^−/−) mice were randomly divided into five groups and fed freely Western diet (WD) which contained ACE (50, 100 and 200 mg/kg) or curcumin (50 mg/kg). The C57/BLJ mice were used as normal and which were fed the WD. After 10 weeks of being fed the WD, the atherosclerosis related mediators and hyperlipidemia induced hepatic steatosis were analyzed in serum, aorta tissue or hepatic tissues.

Results

Ten-week feeding of WD considerably increased the serum lipid profiles including total cholesterol (TC), low density lipoprotein, high density lipoprotein (HDL), triglyceride, TC/HDL ratio and glucose, and also elevated the total reactive oxygen species (ROS) and inflammatory cytokines (tumor necrosis factor-α, TNF-α; and interlukin-6, IL-6) in the serum levels. ACE treatment significantly resolved these alterations. The aortic lesion formation was significantly decreased as were lipid formations by ACE treatment. Moreover, ACE not only caused significant decreases of the lipid drops on the hepatic tissues, but also restored the antioxidant components. The gene expression levels including SREBP‐1c, FAS, SCD‐1, PPAR-α, CPT‐1, IL-6, IL-1β and TNF-α in hepatic tissue were altered by Western diet fed in apoE^−/− mice, while ACE treatment significantly normalized those alterations.

Conclusions

The ACE treatment is beneficial for atherosclerosis in arterial area and hyperlipidemia induced hepatic tissue steatosis.     

Vitexin and isovitexin from the Leaves of Ficus deltoidea with in-vivo α-glucosidase inhibition

Ethnopharmacological relevance

The leaves of Ficus deltoidea are used as a traditional medicine by diabetes patients in Malaysia.

Aim of the study

The objective of the study is to identify and evaluate bioactive constituents with in vivo α-glucosidase inhibition.

Materials and Methods

The partitioned extracts, subfractions and pure bioactive constituents were subjected to α-glucosidase inhibition assay. The identified bioactive constituents were administered orally to sucrose loaded normoglycemic mice and induced diabetic rats. The postprandial blood glucose levels were monitored at 30 min interval. Acute toxicity was evaluated in both normoglycemic mice and induced diabetic rats.

Results

Bioactivity guided fractionation led to the isolation of both vitexin (1) and isovitexin (2). Oral administration of 1 mg/kg of either vitexin (1) or isovitexin (2) significantly (p<0.05) reduced the postprandial blood glucose level in sucrose loaded normoglycemic mice at 30 min. The percentage of postprandial blood glucose reduction was highest in sucrose loaded induced diabetic rats administered orally with 200 mg/kg of vitexin (1) or 100 mg/kg of isovitexin (2). Both vitexin (1) and isovitexin (2) did not exert any signs of toxicity at the highest dose of 2 g/kg administered orally to normoglycemic mice and induced diabetic rats.

Conclusion

Both the C-glycosyl bioflavonoids, namely, vitexin (1) and isovitexin (2) exhibited in vivo α-glucosidase inhibition.     

Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic components

Ethnopharmacological relevance

Panax notoginseng (Burk) F.H. Chen (Araliaceae) is a well-known and commonly used traditional Chinese herb for treatment of various diseases, such as hemostasis, edema and odynolysis.

Aim of study

Our aim was to investigate the mechanisms of anti-hyperglycemic and anti-obese effects of Panax notoginseng saponins (PNS) in KK-Ay mice, and explore the components in PNS for such effects.

Materials and methods

KK-Ay mice received daily intraperitoneal injections of PNS 200 mg/kg or vehicle for 30 days while ginsenoside Re 14 mg/kg, Rd 15 mg/kg, Rg1 40 mg/kg, Rb1 60 mg/kg and notoginsenoside R1 6 mg/kg for 12 days. Fasting blood glucose levels (FBGL), glucose tolerance (GT), serum insulin, leptin levels, body weight changes, food intake, adipose tissues and blood fat levels were measured at different time points.

Results

The PNS group had significantly lower FBGL, improved GT and smaller body weight incremental percentage after the 30-day treatment. Additionally, Rb1 exhibited significant reduction of FBGL on day 12, and Re also exhibited a decreasing trend after the 12-day treatment.

Conclusions

PNS possess anti-hyperglycemic and anti-obese activities by improving insulin- and leptin sensitivity, and Rb1 is responsible for the anti-hyperglycemic effect among the five saponins in KK-Ay mice.     

Chinese medicine tongxinluo significantly lowers serum lipid levels and stabilizes vulnerable plaques in a rabbit model

Relevance to ethnopharmacology

Tongxinluo capsule is a compound preparation formulated on the basis of the meridian theory of traditional Chinese medicine and is officially approved for the treatment of angina pectoris and ischemic stroke in China.

Objectives

To test the hypothesis that the Chinese traditional medicine tongxinluo in capsule form has similar effects as simvastatin in lowering serum lipid levels and stabilizing vulnerable plaques.

Materials and methods

Thirty New Zealand white rabbits underwent balloon-induced abdominal aortic endothelial injury and were fed a diet of 1% cholesterol for 8 weeks. The rabbits were then randomly divided into three groups (n = 10 each) for daily doses of tongxinluo capsule (1 g/kg), simvastatin (5 mg/kg) or no drugs for 12 weeks. At the end of week 20, plaque rupture was induced by pharmacological triggering. Serological, ultrasonographic, pathologic, immunohistochemical, and gene expression studies were performed.

Results

The incidence of plaque rupture with tongxinluo and simvastatin treatment was significantly lower than that with control treatment (0% for both drug treatments vs. 56.0%; P < 0.05). Values of serum lipid profile, inflammatory markers, and pathological and immunohistological assays were significantly improved in the tongxinluo- and simvastatin-treated groups than in the control group. The simvastatin-treated group showed lower serum lipid levels than the tongxinluo-treated group.

Conclusions

Treatment with the Chinese medicine tongxinluo was as effective as simvastatin in lowering serum lipid levels, inhibiting plaque inflammation and preventing vulnerable plaques from rupture and may provide an alternative therapy for atherosclerosis.