Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

The anti-diabetic properties of Guazuma ulmifolia Lam are mediated by the stimulation of glucose uptake in normal and diabetic adipocytes without inducing adipogenesis

ETHNOPHARMACOLOGICAL IMPORTANCE: Guazuma ulmifolia Lam (Sterculiaceae) is a plant extensively used in México for the empirical treatment of type 2 diabetes. AIM OF THE STUDY: To investigate the anti-diabetic mechanisms of Guazuma ulmifolia. MATERIALS AND METHODS: Non-toxic concentrations of Guazuma ulmifolia aqueous extracts (GAE) were assayed on adipogenesis and 2-NBDglucose uptake in the murine 3T3-F442A preadipose cell line. RESULTS: GAE added to adipogenic medium (AM) did not affect adipogenesis at any of the tested concentrations (1-70 microg/ml), whereas in AM lacking insulin GAE 70 microg/ml induced triglyceride accumulation by 23%. On the other hand, GAE 70 microg/ml stimulated 2-NBDG uptake by 40% in insulin-sensitive 3T3-F442A adipocytes and by 24% in insulin-resistant adipocytes, with respect to the incorporation showed by insulin-sensitive adipocytes stimulated with the hormone. CONCLUSION: Guazuma ulmifolia exerts its anti-diabetic effects by stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes without inducing adipogenesis.     

The adjuvant effects of Antrodia Camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells

AIM OF THE STUDY: The objectives of this study were to investigate the adjuvant anti-tumor effects of Antrodia camphorate in human hepatoma cells (C3A and PLC/PRF/5) which are resistance to most anti-tumor agents, elucidate the possible regulation pathways, and measure the tumor growth and survival rate in xenograft-nude mice after combined with anti-tumor agents. MATERIALS AND METHODS: The AC extracts were measured by using a phenol/sulfuric acid method as previously described. The in vitro cell proliferation assay of ACs and anti-tumor agents was tested on C3A and PLC/PRF/5 cell lines. The percentage of human hepatoma cells undergoing apoptosis and distributing in different phases of cell cycle were determined by Flow cytometric analysis. Western blot analysis for MDR-1 and apoptosis- related proteins. The measurements of tumor growth and survival analysis of hepatoma implanted nude mice treated with Antrodia camphorata extracts and anti-tumor agents alone or in combinations. RESULTS: We have found that Antrodia camphorata extracts, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo), which then extended their median survival days. Furthermore, solid-state extracts of Antrodia camphorata (AC-SS) showed its adjuvant effects through the inhibition of MDR gene expressions and the pathway of COX-2- dependent inhibition of p-AKT, which ultimately resulted in the induction of apoptosis in hepatoma cells. CONCLUSIONS: In this study, we have found that Antrodia camphorata extract, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo).     

Antioxidant activity of Antrodia camphorata on free radical-induced endothelial cell damage

AIM OF THE STUDY: Antrodia camphorata (A. camphorata) is well known in Taiwan as a traditional Chinese medicine. The purpose of this study is to evaluate the antioxidant activity of Antrodia camphorata on free radical-induced endothelial cell damage. MATERIALS AND METHODS: In this study, a human umbilical vein endothelial cell (EC) culture system was used to evaluate the effects of the fermented culture broth of A. camphorata (FCBA) and aqueous extracts of mycelia from A. camphorata (AEMA) against the oxidative cell damage induced by the free-radical generator AAPH. RESULTS: The present investigations show that FCBA (25-100 microg/mL) and AEMA (50-200 microg/mL) effectively protect the ECs from damage after exposure to 15 mM AAPH for 16h. However, cell viability was not affected in ECs under controlled conditions after FCBA or AEMA treatment. An increase in EC prostacyclin (PGI(2)) production in response to AAPH exposure was positively and negatively correlated with cell damage and FCBA/AEMA concentration, respectively. Both FCBA and AEMA treatment significantly inhibited AAPH-apoptotic cell death in the ECs, as evidence by reduced DNA fragmentation, cytochrome c release, caspase-3 activation, and dysregulation of Bcl-2 and Bax. Moreover, the AAPH-induced reductions in EC SOD activity and protein levels are prevented by FCBA and AEMA. CONCLUSION: Our findings suggest that A. camphorata possesses antioxidant properties and improves endothelial function, further offering effective protection from atherosclerosis.     

Effects of TGFbeta1 and extracts from Cervus korean TEMMINCK var. mantchuricus Swinhoe on acute and chronic arthritis in rats

AIM OF THE STUDY: To elucidate the pharmacological activities of deer antler acupuncture and TGF61538;1 on the acute and chronic phases of rheumatoid arthritis diseases. MATERIALS AND METHODS: Polyarthritis rats were administered with TGF61538;1 and water extract of deer antler acupunture (DAA), prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe. TGF61538; (0.1 to 2 61549;g/animal) and DAA (5-100 61549;g/kg animal) were initiated 1 day before an arthritogenic dose of streptococcal cell wall fragments to see the effects on the joint swelling and distortion during the acute phase and the chronic phase of the disease. Arthritic index suppression of rat arthritis model was examined by TGF61538; and DAA administrations. RESULTS: TGF61538;1 and DAA diminished the polyarthritis development in rats. TGF61538; and DAA eliminated the joint swelling and distortion observed during the acute phase and the chronic phase of the disease. The TGF61538; and DAA suppressed the arthritis progress when administration was begun after acute phase of arthritis. DISCUSSION: Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF61538;1 and DAA reversed the leukocytosis associated with the chronic phase of the arthritis, respectively.     

Endothelium-independent relaxation and contraction of rat aorta induced by ethyl acetate extract from leaves of Morus alba (L.)

Aim of the study

Based on screening for vasoactive traditional Chinese medicinal herbs, the present study was performed to investigate the vasoactive effects of an ethyl acetate extract from leaves of Morus alba (L.) (ELM) on rat thoracic aorta and the mechanisms underlying these effects.

Materials and methods

Isolated rat thoracic rings were mounted in an organ bath system and the effects of ELM on their responses were evaluated.

Results

ELM (0.125–32.000 g/l) induced a concentration-dependent relaxation (P < 0.01 vs. control) both in endothelium-intact and -denuded aortas precontracted by high K⁺ (6 × 10⁻² M) or 10⁻⁶ M phenylephrine (PE). In endothelium-denuded aortas, ELM at the EC₅₀ concentration reduced Ca²⁺-induced contraction (P < 0.01 vs. control) after PE or KCl had generated a stable contraction in Ca²⁺-free solution. And after incubation with verapamil, ELM induced contraction in endothelium-denuded aortas precontracted by PE (P < 0.01 vs. control); this was abolished by ruthenium red (P < 0.01 vs. ELM-treated endothelium-denuded group; P > 0.05 vs. control), but not by heparin (P > 0.01 vs. ELM-treated endothelium-denuded group; P < 0.01 vs. control).

Conclusions

The results showed that ELM had dual vasoactive effects, and the relaxation was greater than the contraction. The relaxation was mediated by inhibition of voltage- and receptor-dependent Ca²⁺ channels in vascular smooth muscle cells, while the contraction occurred via activation of ryanodine receptors in the sarcoplasmic reticulum.     

Temporal effect of Guanxin No. 2 on cardiac function, blood viscosity and angiogenesis in rats after long-term occlusion of the left anterior descending coronary artery

AIM: Cardiac infarction is one of the main causes of death in both developing and developed countries over past decades. Currently available approaches for treating patients with this disease are not satisfactory. Traditional Chinese medicines have been increasingly paid attention to. The aim of this study was to characterize the dynamic protective effects of Guanxin No. 2 decoction (GX II) on cardiac dysfunction combined with the blood viscosity and myocardial hypertrophy parameters in myocardial infarction (MI) rats. METHODS: Male Sprague-Dawley rats (180-200 g) were randomly divided into three groups: sham-operated, coronary artery ligation (CAL), and CAL plus GX II (GX II, 10.0 g raw materials/kg/d, bid, p.o.). The experiment was carried out at 4 time points as the 3rd, 7th, 14th, and 28th day after ligation. RESULT: It was found that on the one hand, GX II could significantly improve the heart function, and remarkably decrease infarct size and inhibit ventricular remodeling. On the other hand, GX II showed some unique effects such as angiogenesis which was induced in the left ventricular tissue. This result was consistent with the finding of an augmented vascular endothelial growth factor (VEGF) expression in this area. CONCLUSIONS: The studies demonstrated that GX II exerted extensively beneficial cardioprotective effect on CAL rats, it might stimulate angiogenesis of ischemic region to compensate blood supply to the heart via upregulated VEGF expression.