Elevation of intracavernous pressure and NO-cGMP activity by a new herbal formula in penile tissues of aged and diabetic rats

We investigated the mechanisms underlying the effects of an herbal formula (HF) in improving erectile dysfunction (ED), particularly in terms of nitric oxide (NO)-cGMP pathways. Two different rat models, 24-month-old rats (aging) and 10-month-old rats maintained chronically high plasma glucose levels (328 +/- 89 mg/dL) diabetes mellitus (DM), were treated with HF (100 mg/kg per day) for 10 days. We examined the electrostimulated penile responses, expression and activity of three enzymes: neuronal NO synthase (nNOS), endothelial NO synthase (eNOS) and caveolin-1 (CaV-1), and cGMP concentration that act upon the major NO-cGMP signaling pathways in penile tissue. Effect of HF on cGMP degradation was also examined using bovine vascular smooth-muscle cells pretreated with an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In aging and DM rats, the severely reduced peak intracavernous pressures (ICPs) in penile tissues were restored completely after HF treatment, and HF treatment significantly made the latency period earlier. Furthermore, the penile expression levels of nNOS, eNOS and CaV-1, Ca2+ -dependent NOS activities and cGMP concentrations were increased significantly in the HF-treated rats. Particularly, inhibitory effect of HF on cGMP degradation was confirmed also in cell system. These results indicate that new HF originated from a Korean traditional medicine (Ojayounjonghwon described in 'Dong Ui Bo Gam') can ameliorate the ED impaired by peripheral neuropathy and/or angiopathy, via the activation of NO-cGMP pathways.     

降压通脉方对自发性高血压大鼠血压及左心室肥厚的影响

目的:探讨降压通脉方控制血压、逆转高血压左心室肥厚的作用。方法:以自发性高血压大鼠(SHR)为高血压及高血压左心室肥厚模型,随机分为降压通脉方组、卡托普利组、空白对照组;并以WKY大鼠为正常对照组。检测大鼠尾动脉收缩压(SBP)、大鼠左室质量(LV)、左心室质量指数(LVMI)、左室壁相对厚度。结果:与模型组比较,中药组于药后第4周出现血压下降,降压效果于第14周达到与西药相比无明显差异。模型组、中药组、西药组LVMI较正常组明显升高,提示左室肥厚形成,中药组、西药组左室壁相对厚度较模型组室壁薄,提示降压通脉方有逆转左室肥厚的作用。结论:降压通脉方可有效地降低SHR血压,有一定逆转SHR左心室肥厚的作用。     

黄连解毒汤对自发性高血压大鼠血压和炎症因子的影响

目的:观察黄连解毒汤对自发性高血压大鼠(SHR)血压和炎症因子的影响,探讨黄连解毒汤治疗高血压的机制。方法:雄性12周龄SHR 24只随机分为黄连解毒汤组、模型对照组和卡托普利组3组,治疗6周,检测治疗前后的血压变化,测定血清中超敏C-反应蛋白(hs-CRP)、6酮前列环素(6-K-PG)、NO、内皮素-1(ET-1)、血管性血友病因子(vWF)、同型半胱氨酸(Hcy)和单核细胞趋化因子(MCP-1)变化,并以同龄Wistar Kyoto(WKY)大鼠8只做空白对照组。结果:SHR血压呈进行性增高,血清中hs-CRP、ET-1、vWF、Hcy和MCP-1升高,NO和6-K-PG降低(P<0.05,P<0.01),黄连解毒汤可控制SHR血压,降低hs-CRP、ET-1、vWF、Hcy和MCP-1,增加NO和6-K-PG(P<0.05,P<0.01)。结论:黄连解毒汤可通过调节炎症因子水平,控制SHR高血压的发展。     

Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats

The antiosteoporotic effect of a herbal formula, Er-Xian Decoction (EXD), in ovariectomized (OVX) rats model of osteoporosis was investigated. The rats were divided into Sham and OVX groups. The OVX rats were further sub-divided into four groups administered orally with water, nylestriol (1 mg/kg, weekly) or EXD (300, 600 mg/kg, daily) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by EXD treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with EXD and nylestriol. In addition, EXD completely corrected the decreased concentration of calcium, phosphorus, and estradiol in serum observed in OVX rats. EXD also significantly increased biomechanical strength comparable to the Sham group. This was also confirmed by histological results that showed its protective action. The findings assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters strongly suggested that EXD had a definite antiosteoporotic effect, which is similar to estrogen.     

Effects of Xin-Ji-Er-Kang formula on 2K1C-induced hypertension and cardiovascular remodeling in rats

Ethnopharmacological relevance

Xin-Ji-Er-Kang (XJEK), a Chinese herbal formula, is effective against hypertension induced coronary heart disease, viral myocarditis and toxic myocarditis. In this study, the effect of XJEK on cardiovascular system was investigated. To test the hypothesis that Xin-Ji-Er-Kang (XJEK) has an anti-hypertensive effect mediated through attenuation of cardiac remodeling, and amelioration of vascular endothelial dysfunction and oxidative stress.

Materials and methods

Hypertension was induced in Wistar rats by 2 kidney 1 clip (2K1C) treatment. The hypertensive rats were then randomly assigned into four groups and treated as follows: group 1 (Sham-operated [Sh-Op] group received only drinking water), group 2 (induced hypertensive model+no treatment), and group 3 (induced hypertensive+a single daily oral dose of 24 g kg⁻¹ XJEK treatment) and group 4 (induced hypertensive+a single oral dose of 15 mg kg⁻¹ Fosinopril treatment). The rats in all the defined groups were respectively treated for a period of 4 weeks. Cardiovascular parameter such as systolic blood pressure (SBP) was measured weekly by using tail-cuff apparatus; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the rate of the rise in left ventricular pressure (±dp/dt max) were measured by using a PowerLab 8/30 apparatus (AD Instruments, Australia) at the end of the 8th week; heart weight/body weight (HW/BW) was determined as an index of myocardial hypertrophy (MH). Hematoxylin and eosin (H&E) and Van Gieson (VG) stain were used to assess the cardio-histological changes. Colorimetric analysis was used to assay serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), nitric oxide (NO), and hydroxyproline (Hyp) contents in cardiac tissue. Angiotensin II (Ang II) content in serum was assessed by radioimmunoassay; tetrahydrobiopterin (BH₄) content in cardiac tissue, BNP and endothelial NOS (eNOS) in serum were determined by using ELISA, and the protein expressions of c-Jun NH2-terminal kinase (JNK), P-JNK, p38, P-p38, and NADPH oxidases-2 (Nox-2) were measured by western blot.

Results

XJEK therapy could impair the heart systolic and diastolic function, potently improve the heart weight index, inhibit the elevation of HW/BW ratio, and markedly ameliorate hemodynamic indices and vascular remodeling index. It has blunted the decrease of SOD, NO and the increase in MDA and Ang II serum contents, myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) compared to the hypertensive model group. It also reduced the serum content of Hyp while increased BH4 levels in cardiac tissue. In addition, the expressions of Nox-2, P-JNK and P-p38MAPK were all suppressed compared to the hypertensive model group. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting eNOS activities and enhancing the NO activity in serum.

Conclusion

The results of the present study show that XJEK attenuates 2K1C-induced hypertension in rats, which confirms our hypothesis that XJEK has an anti-hypertensive and cardiovascular remodeling effect via attenuation of cardiac remodeling and improvement of endothelial dysfunction and oxidative stress.     

The effects of acupuncture on cardiac muscle cells and blood pressure in spontaneous hypertensive rats

If acupuncture is able to prevent hypertrophy of the heart, it could therefore prevent the heart from overloading and thus prevent heart failure or sudden death. We therefore studied the effects of acupuncture on blood pressure and cardiac muscle cells. Rats with spontaneous hypertension were divided into three acupuncture treatment groups and one non-treatment group. The treatment groups were classified as sham acupoint, Yanglingquan (GB. 34) and Quchi (LI. 11) groups. The measurements recorded included changes in tail pressure, femoral arterial pressure, left ventricular weight (LVW), whole heart weight (WHW), body weight (BW), LVW/BW and WHW/BW ratios and the size of the cardiac muscle cells. The results showed that femoral arterial pressure of subjects which were needled on the selected points for 3 days dropped. Acupuncture at these two acupoints seemed to improve the condition of hypertension in a short period of time. Significant changes in the femoral arterial pressure were observed in all subjects when they were treated for 6 days. In the two acupoint groups, the LVW/BW and the WHW/BW ratios did not change significantly. Cardiac muscle cells reduced in size in the Yanglingquan (GB. 34) treatment groups. This indicates that the Yanglingquan (GB. 34) points not only can lower blood pressure, but also prevent hypertrophy of cardiac muscle cells in spontaneous hypertensive rats (SHR). Therefore, acupuncture could be a good treatment modality for hypertension and hypertrophy of the heart.     

Antifibrotic effects of CGX,a traditional herbal formula,and its mechanisms in rats

Aim

CGX is a modification of a traditional herbal medicine for “liver cleaning,” which is used to treat various chronic liver disorders in oriental clinics. This study investigated the antifibrotic effects and associated mechanisms of CGX.

Materials and methods

Liver fibrosis was induced in rats by dimethylnitrosamine (DMN; 10 mg kg⁻¹, ip) injection on 3 consecutive days per week for 4 weeks. CGX (100 or 200 mg kg⁻¹, po) was administrated once a day for 4 weeks. Three cell lines (HepG2, RAW 264.7, and HSC-T6) were used to examine its mechanisms.

Results

CGX treatment dramatically ameliorated the change in liver and spleen weight and serum albumin (p < 0.01), aspartate transaminase (p < 0.01), alanine transaminase (p < 0.01), alkaline phosphatase (p < 0.01), and total bilirubin (p < 0.01) levels. Histopathologically, CGX administration decreased necrosis, inflammatory cell infiltration, and collagen accumulation. The antifibrotic effects of CGX were confirmed from hydroxyproline determination and the reduction in the numbers of activated hepatic stellate cells. In addition, antioxidant proteins, glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities were maintained in the CGX-treated groups compared with the DMN group. CGX downregulated fibrosis-related genes (inducible nitric oxide synthase, tumor necrosis factor-alpha, transforming growth factor-beta, connective tissue growth factor, and platelet-derived growth factor-beta) and decreased the protein levels of profibrotic cytokines (transforming growth factor-beta and platelet-derived growth factor-beta) in liver tissues. In the cell line-based studies, CGX showed supportive effects, such as the protection of hepatocytes from CCl₄-toxicity, inhibition of NO production in RAW 264.7 cells, and inactivation of hepatic stellate cells.

Conclusion

These results demonstrated the antifibrotic effects of CGX and the corresponding mechanisms associated with sustaining the antioxidative system and inhibiting hepatic stellate cell activation via the downregulation of fibrogenic cytokines.     

Effects of osthol on blood pressure and lipid metabolism in stroke-prone spontaneously hypertensive rats

Osthol, a coumarin compound, was isolated from the dried fruits of Cnidium monnieri (Umbelliferae) and the effect of dietary osthol on hypertension and lipid metabolism was examined in stroke-prone spontaneously hypertensive rats (SHRSP). Six-week-old male SHRSP were fed the experimental diet containing 0.05% osthol by weight for 4 weeks with free access to the diet and water. Elevation of systolic blood pressure was significantly suppressed on and after 3 weeks. In addition, significant decreases in cholesterol and triglyceride contents in the liver were recognized without any significant changes in serum lipids profiles. A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids. This may be responsible, at least in part, for the reduction of hepatic triglyceride content in SHRSP. These beneficial effects of osthol could be useful for both prevention of atherosclerosis and suppression of hepatic lipid accumulation.     

Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

Ethnopharmacological relevance

Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family Alliaceae, most commonly associated with onions and garlic. In South Africa, this herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension and stomach problems. The aim of this study was to evaluate the effect of methanol leaf extracts (MLE) of Tulbaghia violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats; and to find out the mechanism(s) by which it acts.

Materials and methods

The MLE of Tulbaghia violacea (5–150 mg/kg), angiotensin I human acetate salt hydrate (ang I, 3.1–100 μg/kg), angiotensin II human (ang II, 3.1–50 μg/kg), phenylephrine hydrochloride (phenylephrine, 0.01–0.16 mg/kg) and dobutamine hydrochloride (dobutamine, 0.2–10.0 μg/kg) were infused intravenously, while the BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab.

Results

Tulbaghia violacea significantly (p < 0.01) reduced the systolic, diastolic, and mean arterial BP; and HR dose-dependently. Ang I, ang II, phenylephrine and dobutamine all increased the BP dose-dependently. The hypertensive effect of ang I and the HR-increasing effect of dobutamine were significantly (p < 0.01) decreased by their co-infusion with Tulbaghia violacea (60 mg/kg). However, the co-infusion of ang II or phenylephrine with Tulbaghia violacea (60 mg/kg) did not produce any significant change in BP or HR when compared to the infusion of either agent alone in the same animal.

Conclusions

Tulbaghia violacea reduced BP and HR in the SHR. The reduction in BP may be due to actions of the MLE on the ang I converting enzyme (ACE) and β₁ adrenoceptors.     

The effect of continuous Jue tone intervention on blood pressure and vasoactive substances in hypertensive rats with a liver-fire hyperactivity pattern

ObjectiveJue tone is a kind of sound, using 3-mi as the main tone, and is melodious, profound, makes people feel comfortable and pleasant. This study aimed to explore the probable mechanism of Jue tone to reduce blood pressure (BP) in hypertensive rats with a liver-fire hyperactivity pattern by observing changes in BP as well as physiochemical indexes in plasma.MethodsSixteen male spontaneous hypertensive rats (SHR) with a liver-fire hyperactivity pattern were randomly divided into a control group and a Jue tone group. The rats in the Jue tone group were treated with Jue tone (55–65 dB, played by the five elements of music rhythm instrument, a kind of physiotherapy regimen music played by Shen Wu) once a day for 4 weeks. The BP levels in each group were measured twice a week, on Monday and Friday. The levels of angiotensin II (Ang- II), thromboxane B2 (TXB2), endothelin-1 (ET-1), calcitonin gene-related peptide (cGRP), norepinephrine (NE), cortisol (CORT), and 5-hydroxytryptamine (5-HT). in plasma were detected by enzyme-linked immunosorbent assay after 4 weeks of intervention.ResultsBP and the levels of TXB2 and ET-1 in the plasma of the treatment group were significantly lower than those of the control group, while the level of cGRP was significantly higher.ConclusionJue tone can reduce the BP of hypertensive rats with a liver-fire hyperactivity pattern. The mechanism may correlate with a reduction in TXB2 and ET-1 and an increase in cGRP with the reduction of reactive oxygen species (ROS).     

Protective effect of Bojungikki-tang, a traditional herbal formula, against alcohol-induced gastric injury in rats

Ethnopharmacological evidence

Oxidative stress plays an important role in the pathogenesis of ethanol-induced acute gastric mucosal injury. Bojungikki-tang (Hochuekkito in Japanese, Bu-zhong-yi-qi-tang in Chinese) is a traditional herbal formula used in Korea, Japan, and China to treat allergic diseases and gastrointestinal disorders. However, the mechanism responsible for its actions has not been investigated experimentally.

Aim of the study

The aims of this study were to investigate whether Bojungikki-tang water extract (BJITE) has protective effects against ethanol-induced acute gastric injury in rats and to perform an acute toxicity study to evaluate its safety.

Materials and methods

In this rat model, gastric mucosal injury was imposed by oral administration of 5 mL/kg body weight of absolute ethanol. BJITE at one of two doses (200 or 400 mg/kg body weight) was administered by gavage 2 h before ethanol administration. Gastric tissues were collected and analyzed to assess the gastric injury index, and content or activity of catalase, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx).

Results

Acute administration of ethanol significantly increased the gastric injury index concomitantly with an increase in MDA and GSH content, and a decrease in the activities of catalase, GST, GR, GPx, and SOD. Pretreatment with 200 or 400 mg/kg BJITE attenuated ethanol-induced gastric mucosal injury; this was accompanied by an increase in the content or activity of PGE₂, catalase, GSH, GST, GR, GPx, and SOD, and a decrease in MDA content. In the acute toxicity study, no adverse effects of BJITE were observed at doses up to 2000 mg/kg body weight.

Conclusion

These results indicate that BJITE can partly protect the gastric mucosa from ethanol-induced acute gastric injury and suggest that these protective effects might be induced by increasing the antioxidant status. We suggest that BJITE can be developed as an effective drug for the treatment of acute gastric injury.     

Suppression of the onset and progression of collagen-induced arthritis in rats by QFGJS, a preparation from an anti-arthritic Chinese herbal formula

QFGJS is an herbal preparation, and its pronounced effectiveness in treating adjuvant-induced arthritis (AIA) has been previously demonstrated. We herein aimed to confirm its anti-arthritic effect on collagen-induced arthritis (CIA) in rats. CIA was established in female Wistar rats with intradermal injection of type II bovine collagen at the base of the tail of animals. CIA rats were treated daily with oral administration of different doses of QFGJS beginning on the day of the induction of arthritis (day 0, the prophylactic treatment) or on the day after the onset of arthritis (day 13, the therapeutic treatment) until day 30. The results showed that prophylactic treatment with QFGJS significantly suppressed the onset of arthritis, and therapeutic treatment with QFGJS markedly reduced paw swelling and ESR levels even in the established CIA. Radiologic and histopathologic changes in the arthritic joints were also significantly reduced in the QFGJS-treated versus vehicle-treated rats. Moreover, the serum levels of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were markedly lowered in the QFGJS-treated rats. Hence, our studies demonstrate the quality, safety, and effectiveness of QFGJS as an anti-arthritic agent, which makes QFGJS a strong candidate for further clinical trials on rheumatoid arthritis (RA) patients.     

Blood pressure lowering effect of the aqueous extract of the stem of Ipomoea acanthocarpa (convolvulaceae) in spontaneously and salt-loaded hypertensive rats

Spontaneously hypertensive (SHR) and salt-loaded hypertensive rats (SLHR) were submitted to a daily treatment by gavage of 2 mL/100 g body weight of the aqueous extract of the stem of Ipomoea acanthocarpa (30 mg/mL stock solution). A fall in blood pressure of nearly 13% was observed after two successive administrations of the aqueous extract. After 14 days of treatment, the blood pressure fell by more than 30±8%. The hypotensive effect might be due to a direct vascular smooth muscle effect or to its already observed high diuretic effects or might be acting by some other mechanism.     

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats

ObjectiveTo investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).MethodsEight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.ResultsEA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.ConclusionEA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.     

Liuwei Dihuang,a traditional Chinese herbal formula,suppresses chronic inflammation and oxidative stress in obese rats

OBJECTIVE: To investigate the anti-infl ammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang(LWDH), a traditional Chinese herbal formula, in obese rats. METHODS: After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-derived(OP-CD) rats were fed a modified AIN-93 G diet containing 60% energy from fat. Treatment was performed twice daily by gavage feeding with 500, 1 500, or 3 500 mg/kg body weight LWDH suspended in water(n=12 rats per group). Twelve obese-resistant-CD(OR-CD) rats were fed the atherogenic diet and gavaged with water, and served as the normal control. Blood biomarkers of inflammation, oxidative stress and adiponectin were measured post-sacrifi ce and used to determine the treatment effect of LWDH and assess the suitability of OR/OP-CD rats for studying these parameters. RESULTS: After 9 weeks of treatment, LWDH lowered serum C-reactive protein(CRP) and tumour necrosis factor-α(TNF-α) levels. Serum interleukin-6(IL-6) levels showed a tendency towards reduction, but were not signifi cantly different from the OP-CD control. Liver superoxide dismutase(SOD) activity was increased in response to all three doses of LWDH, while the levels of reduced(GSH) and oxidized glutathione(GSSG) and thiobarbituric acid reactive substances(TBARS) were unchanged. Serum adiponectin levels were increased in response to oral administration of LWDH at the dose of either 500 or 1 500 mg/kg body weight. In addition, comparisons between OR-CD and OP-CD rats revealed differential, and for some biomarkers, conflicting characteristics of high-fat diet-fed OP-CD rats in reference to obese human subjects in terms of infl ammatory and oxidative stress biomarkers and circulating adiponectin levels. CONCLUSION: The results show, for the fi rst time, the anti-infl ammatory, anti-oxidative stress and adiponectin-ameliorating effects of LWDH in obese rats. The suitability of the OR/OP-CD rat model as a research tool to study infl ammation, oxidative stress, and adipokine production requires further investigation.     

加味脉君安片对自发性高血压大鼠血压的影响及其机制研究

Objective: Maijunan(MJA) Tablets is a protected variety of traditional Chinese medicine(TCM) consisted of Pueraria lobata, hydrochlorothiazide(HTCZ), Uncaria rhynchophylla(366:1:980) and excipient. In the present work, MJA was consisted of the total flavones of P. lobata, HCTZ and total alkaloids of U. rhynchophylla(40:11:75). The combination of MJA and the total phenols of Magnolia officinalis(M-MJA) was consisted of the total flavones of P. lobata, the total phenols of M. officinalis, HCTZ and the total alkaloids of U. rhynchophylla(40:40:11:75). The aim of this work was to examine the effect and mechanism of M-MJA on the blood pressure of spontaneous hypertensive rats(SHRs).Methods: Adult male SHRs were randomly divided into control group, MJA group(180 mg/kg·d), and the M-MJA group(218 mg/kg·d)(n = 5). SHRs were orally administered with M-MJA and MJA respectively once a day for 8 weeks, the blood pressure of SHRs was measured every two weeks, and the biochemical indicators related to blood pressures were detected at the last dosing.Results: After oral administration of M-MJA to SHRs once a day for 8 weeks, the systolic and diastolic blood pressures of SHRs were deceased significantly. M-MJA affected renin-angiotensin-aldosterone system by decreasing the levels of Ren, Ang II and ALD, affected the endothelial function by decreasing the levels of ET-1 and 20-HETE, and increasing the level of eNOS, affected the oxidative stress by increasing the protein expression of Nrf2 and the activities of HO-1 and GSH-Px, and decreasing the protein expression of CYP2 E1 and CYP4 A, as well as the content of MDA.Conclusion: These results indicated that M-MJA could regulate the renin-angiotensin-aldosterone system,improve endothelial function, and inhibit CYP4 A activity to reduce the production of 20-HETE, alleviate the oxidative stress disorder of the visceral organs, and eventually exert antihypertensive effect. Additionally, the anti-oxidant ability, regulating the renin-angiotensin-aldosterone system and improving endothelial function of M-MJA are more powerful than that of MJA, suggesting that M-MJA may have a better anti-hypertensive effect than MJA.     

天麻钩藤饮对自发，陡高血压大鼠血压干预及血清酶活，陡影响研究

目的：本课题旨在探讨天麻钩藤饮对自发性高血压大鼠（SHR）的血压抗氧化血清酶的活性变化及血清钙离子浓度的影响,以期进一步阐明天麻钩藤饮对血压干预的作用机制,为中医药防治高血压提供实验依据。方法：选用12周龄自发性高血压雄性大鼠随机分组。治疗4w后,测量收缩压;使用紫外分光光度计测定血清T-SOD（CuZn-SOD）、GSH-PX、MDA指标的活力变化;并用全自动图像分析系统进行分析;测定血清游离钙浓度。结果：①天麻钩藤饮组用药4W后与实验前SHR血压下降最明显（P〈0．01）;②天麻钩藤饮组和天麻钩藤饮去石决明组T-SOD、CuZn-SOD、GSH-PX的含量增高及MDA的含量与生理盐水对照组比较有统计学意义（P〈0．05）,以天麻钩藤饮组改变最明显（P〈0．01）;③用药前后天麻钩藤饮组和硝苯地平组血清游离钙浓度没有比实验用药前降低,浓度改变均没有统计学意义（P〉0．05）。结论：①天麻钩藤饮和硝苯地平能够抑制早期的高血压,天麻钩藤饮长期降压效果优于硝苯地平;②天麻钧藤饮的抗氧化,清除超氧自由基作用明显优与钙拮抗剂硝苯地平和石决明;③天麻钩藤饮对血压的干预机制清除血管超氧自由基抗血管氧化作用、阻滞血管平滑肌细胞钙离子浓度作用的多靶点、多层次、多途径的共同发挥干预血压的作用。     

Effects of SYJN,a Chinese herbal formula,on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats

Aim of the study

Suyu-Jiaonang (SYJN) is a Chinese herbal formula that contains four herbs: Bupleurum chinense DC, Curcuma aromatica Salisb., Perilla frutescens (Linn.) Britt., and Acorus tatarinowii Schott. Previous studies conducted in our laboratory have revealed an antidepressant-like effect of the formula in various mouse models of behavioral despair. The present study aimed to investigate whether SYJN could produce antidepressant-like effects in chronic unpredictable stress (CUS)-induced depression model in rats and its possible mechanism(s).

Materials and methods

Rats were subjected to an experimental setting of CUS. The effect of SYJN treatment on CUS-induced depression was examined using behavioral tests including the sucrose consumption and open field tests. The mechanism underlying the antidepressant-like action of SYJN was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats.

Results

Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption and locomotor activity (assessed in the open field test). In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily intragastric administration of SYJN (1300 or 2600 mg/kg) during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex.

Conclusion

The results suggest that SYJN alleviates depression induced by CUS. The antidepressant-like activity of SYJN is likely mediated by the increase in BDNF expression in brain tissues.     

Combined antihypertensive effect of luteolin and buddleoside enriched extracts in spontaneously hypertensive rats

Ethnopharmacological relevance

Flos Chrysanthemi is used in a variety of diseases in traditional Chinese medicine including hypertension, and the total flavonoids (rich in luteolin (LUT) and buddleoside (BUD)) of Flos Chrysanthemi is known to modulate vascular functions and reduce the blood pressure. However, the active flavonoids and their synergistic effects on anti-hypertension are still unclear. To investigate the combined anti-hypertension effects of LUT and BUD enriched extracts on spontaneously hypertensive rats (SHR), as well as the anti-hypertensive mechanism of LUT&BUD mixture.

Materials and methods

CODA Mouse & Rat Tail-Cuff Blood Pressure System was used to measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR after treated with extracts contains with LUT and/or BUD. The expressions of Ang II, PRA, ALD, ET, PGI₂ and TXB₂ were investigated by ELASA. Serum NO concentration was measured by the method of Nitric acid reductase.

Results

A single administration of LUT, BUD, or LUT:BUD=1:1 significantly reduced SBP by about 3.35 mmHg, 4.39 mmHg and 15.42 mmHg, respectively. Chronic administration of LBM (at 60 mg/kg; p.o. for 30 days) reduced both SBP and DBP by 4.04% and 5.24% of the vehicle group, respectively. Oral administration of LBM at 60 mg/kg inhibited the serum levels of ANG, ALD and ET, but increased serum NO concentration.

Conclusion

This study shows the synergistic anti-hypertension effects of LUT and BUD in SHR. The effects of LBM on blood pressure are associated with RAAS and endothelial system. Thus, our experiments suggest that the combination of luteolin and buddleoside from Flos Chrysanthemi are potentially useful for the therapeutic treatments for hypertension.